The Effect of PCSK9 Inhibitors on LDL-C Target Achievement in Patients with Homozygous Familial Hypercholesterolemia: A Retrospective Cohort Analysis.

INTRODUCTION: Achieving target low-density lipoprotein-cholesterol (LDL-C) levels remains challenging when treating homozygous familial hypercholesterolemia (HoFH). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are prescribed in addition to statins and ezetimibe, but patients' response varies and depends on residual low-density lipoprotein receptor (LDLR) function. METHODS: A multicenter, retrospective observational analysis evaluated LDL-C target achievement in response to PCSK9i treatment in 28 patients with HoFH from the Middle East/North Africa region. Effect of genotype was investigated. Demographic and clinical information was retrospectively obtained from medical records. Patient response to PCSK9i treatment was assessed by calculating percentage changes in lipid levels from pre-PCSK9i treatment baseline to most recent follow-up visit where patients were recorded as receiving PCSK9i on top of standard of care lipid-lowering therapies (LLTs; i.e., statins/ezetimibe) and assessing European Atherosclerosis Society (EAS) target achievement up to January 31, 2022. Lowest LDL-C level while receiving PCSK9i was identified. RESULTS: The cohort (n = 28) had a mean age (standard deviation; SD) of 22.8 (9.8) years (n = 28) and was 51% female (n = 27). Baseline LDL-C data were available in 24/28 (85.7%) patients (mean [SD] 14.0 [3.0] mmol/L). Median (interquartile range) duration of PCSK9i treatment was 12.0 months (4.0-19.1) months and mean (SD) % change in LDL-C after PCSK9i treatment was - 8.6% (12.1). LDL-C reduction from baseline was below 15% in 17/24 patients (70.8%). In the full cohort, mean (SD) minimum LDL-C during PCSK9i treatment was 11.9 (2.8; n = 28) mmol/L. No patient achieved EAS target LDL-C while receiving PCSK9i; genotype analysis suggested LDLR-null/null patients were most refractory to PCSK9i. CONCLUSION: Response to PCSK9i was minimal in this cohort of patients with HoFH. No patients achieved EAS LDL-C targets, and most failed to reach the EAS-recommended 15% LDL-C reduction for PCSK9i therapy continuation. These results suggest additional LLTs are necessary to achieve LDL-C targets in HoFH.

Transplantation of heterozygous familial hypercholesterolemia living donor liver resulting in early myocardial infarction: a possible dangerous link.

Living donor liver transplantation (LDLT) is a lifesaving procedure that is often curative for several liver diseases. Familial hypercholesterolemia (FH) is a metabolic disease that results from an autosomal dominant mutation in the low-density lipoprotein receptor; yet, young patients with FH can live years without detection. Herein, we report a case of a patient who developed early myocardial infarction (MI) after having a transplant from a donor with undetected heterozygous FH. This was a 67-year-old female with non-alcoholic steatohepatitis-related liver cirrhosis, free from coronary artery disease, who underwent LDLT from her daughter, a 45-year-old female with no past medical history. One year post-transplant, she presented with an acute MI with a large atherosclerotic burden. Genetic analysis confirmed heterozygous FH in the donor but not in the recipient. This case emphasizes the importance of incorporating a thorough clinical history and lipid profile into pre-transplant testing for both the recipient and donor, as well as aggressive lipid-lowering therapy post-transplantation to avoid cardiovascular complications.

The Ross Procedure: Imaging, Outcomes and Future Directions in Aortic Valve Replacement.

The Ross procedure is gaining recognition as a significant option for aortic valve replacement (AVR), and is particularly beneficial in specific patient groups. Although categorized as a class IIb recommendation in the 2020 American College of Cardiology (ACC)/American Heart Association (AHA), and the European Society of Cardiology (ESC) management guidelines on valvular heart disease, recent studies bolster its credibility. Research, including a propensity-matched study, underlines the Ross procedure's association with enhanced long-term survival and reduced adverse valve-related events compared to other AVR types. This positions the Ross procedure as a primary option for AVR in young and middle-aged adults within specialized centers, and potentially the only choice for children and infants requiring AVR. This review meticulously examines the Ross procedure, covering historical perspectives, surgical techniques, imaging, and outcomes, including hemodynamic performance and quality of life, especially focusing on pediatric and young adult patients. It explores contemporary techniques and innovations like minimally invasive approaches and tissue engineering, underscoring ongoing research and future directions. A summarization of comparative studies and meta-analyses reiterates the Ross procedure's superior long-term outcomes, valve durability, and preservation of the left ventricular function, accentuating the crucial role of patient selection and risk stratification, and pinpointing areas for future research.

Modern approaches to the management of homozygous familial hypercholesterolemia in the Middle East and North Africa.

Homozygous familial hypercholesterolaemia (HoFH) is a severe form of FH in which inheritance of two defective or null mutations in genes associated with metabolism of low-density lipoprotein cholesterol (LDL-C) results in extremely high LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) and mortality. Treatment of HoFH comprises a multi-modal approach of statins, ezetimibe, lipoprotein apheresis; and inhibitors of proprotein convertase subtilisin/kexin type, angiopoietin-like protein 3 (ANGPTL3) and microsomal triglyceride transfer protein. These treatments are generally costly, and patients also often require treatment for ASCVD consequent to HoFH. Therefore, in the interests of both economics and preservation of life, disease prevention via genetic screening and counselling is rapidly becoming a key element in the overall management of HoFH. Guidelines are available to assist diagnosis and treatment of HoFH; however, while advancements have been made in the management of the disease, there has been little systematic attention paid to prevention. Additionally, the Middle East/North Africa (MENA) region has a higher prevalence of HoFH than most other regions - chiefly due to consanguinity. This has led to the establishment of regional lipid clinics and awareness programs that have thrown education and awareness of HoFH into sharp focus. Incorporation of principles of prevention, education, awareness, and data from real-world use of existing therapeutics will significantly enhance the effectiveness of future guidelines for the management of HoFH, particularly in the MENA region.

The hidden unicuspid: Recurring aortic stenosis post-valvuloplasty from a unicuspid aortic valve masquerading as bicuspid.

Unicuspid aortic valves (UAV) account for 0.2 % of cardiac valvular disorders and present with early-onset aortic stenosis (AS) during adolescence or early adulthood. We present a case of a 17-year-old male with recurring AS. He was diagnosed with bicuspid aortic valve (BAV) two years previously and treated with balloon valvuloplasty, which relieved symptoms before that. Multimodality imaging work-up revealed the precise morphology of UAV, consistent with the surgical findings. The patient received a St. Jude mechanical valve (St Paul; MN, USA) which resolved his symptoms. A thorough radiologic evaluation is therefore required for the accurate diagnosis of UAVs. While 2-dimensional (2D) transthoracic echocardiography (TTE) often constitutes the initial modality for evaluating UAVs, 3D-TTE, transesophageal echocardiography, and cardiac computed tomography are used as confirmatory diagnostic tools. Balloon valvuloplasty reports good outcomes in BAV but is associated with an increased rate of symptom recurrence, repeated surgical procedures, and higher mortality in UAVs, underscoring the importance of an accurate pre-operative diagnosis. Learning objectives: 1.Unicuspid aortic valve (UAV) should be considered in the differential diagnosis of severe aortic stenosis during childhood.2.3D-transthoracic echocardiogram, transesophageal echocardiogram, and cardiac computed tomography (CT) can confirm the diagnosis of a UAV.3.Cardiac CT can additionally assess for accompanying abnormalities of the great vessels in UAV patients.4.Balloon valvuloplasty reports good outcomes in bicuspid aortic valve but is associated with an increased rate of symptom recurrence in UAV patients.

Role of three-dimensional transesophageal echocardiography in cardiac myxomas: an imaging challenge.

Nowadays, the diagnosis of cardiac myxomas (CM), particularly the histological types, remains a challenge. Two-dimensional (2D) transthoracic (TT) and transesophageal (TEE)  echocardiography (ECHO) represent the first steps in the imaging pathway. 3D ECHO,  implemented in imaging practice, appears to be an emerging diagnostic technique that overcomes some of the limitations of 2D ECHO while integrating the information provided by magnetic resonance (MRI). However, its role in the imaging arena is still debatable. Analyzing 17 myxomas in 13 patients, the study uncovers a diverse anatomical spectrum. Classical CM morphology is a minority, with most myxomas being sessile and originating from unexpected locations (right ventricular outflow tract and left atrial appendage). Texture and size variations are also noted. Comparing imaging, 2D TEE outperforms 2D TT in visualizing anatomical features, especially attachment types. 3D TEE confirms 2D TT findings and offers more detailed assessments, identifying peduncles missed in four cases by 2D TEE. Two small recurrent myxomas were exclusively detected by 3D TEE, not by 2D TEE or MRI. Two patients have papillary myxomas, one has an embolism. Another patient with a solid myxoma also suffers an embolism, with a clot found at the apex during surgery. Our study showed that CM has a wide anatomical spectrum beyond the typical features, making the diagnosis challenging. Therefore, a multimodality imaging approach is essential for distinguishing CM from other cardiac masses and differentiating myxoma histological types. These findings stress the importance of incorporating 3D ECHO alongside other imaging techniques for a comprehensive evaluation.

Unlocking insights in bicuspid aortic valve management in adult patients: the vital role of cardiac imaging.

The bicuspid aortic valve (BAV) presents a multifaceted clinical challenge due to its diverse morphologies and associated complications. This review aims to elucidate the critical role of cardiac imaging in guiding optimal management strategies for BAV patients. BAV, with a prevalence of 1-2%, has genetic underpinnings linked to the NOTCH1 gene mutation. Variability in BAV morphology necessitates tailored surgical approaches. The three primary types of BAV morphology - right-left cusp fusion, right-noncoronary cusp fusion, and left-noncoronary cusp fusion - demand nuanced considerations due to their distinct implications. Valvular dysfunction results in aortic stenosis or regurgitation, attributed to altered valve structure and turbulent hemodynamics. Cardiac imaging modalities, including echocardiography, magnetic resonance imaging, and computerized tomography, are instrumental in assessing valve function, aortic dimensions, and associated complications. Imaging helps predict potential complications, enabling informed treatment decisions. Regular follow-up is crucial to detecting alterations early and intervening promptly. Surgical management options encompass aortic valve repair or replacement, with patient-specific factors guiding the choice. Post-surgical surveillance plays a vital role in preventing complications and optimizing patient outcomes. The review underscores the significance of advanced cardiac imaging techniques in understanding BAV's complexities, facilitating personalized management strategies, and improving patient care. By harnessing the power of multimodal imaging, clinicians can tailor interventions, monitor disease progression, and ultimately enhance the prognosis and quality of life for individuals with BAV.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Management and clinical outcomes of patients with homozygous familial hypercholesteremia in Saudi Arabia.

We report the incidence, patient characteristic with clinical outcomes in patients with homozygous familial hypercholesterolemia (HoFH) in Saudi Arabia. This is a retrospective and prospective, single center study which included 37 patients 14 years and older enrolled and followed up between 2018-2021 for three years. 46% were females, 78% were offspring of consanguineous marriage. LDLR mutation was in 78% and LDL-C/LDLRAP in 3% of patients. Mean LDL-C at the first presentation was 14.2±3.7 mmol/L, average Dutch lipid score was 20.9±6.24. LDL apheresis was performed on 70% of patients. Most patients were on ezetimibe (92%), high-dose statins ( 84%) and  PCSK9 inhibitors (32%). 48.6% had aortic stenosis, out of which 30% had severe aortic stenosis. Ten underwent aortic valve surgery (5 mechanical valve, 3 Ross procedure, 1 aortic valve repair, 1 bioprosthetic valve) and one had transcatheter aortic valve implantation (TAVI). Coronary artery bypass surgery (CABG) was performed on 32% and percutaneous intervention (PCI) on 11% of patients. HoFH patients have complex diseases with high morbidity and mortality, and benefit from a highly specialized multidisciplinary clinic to address their clinical needs. Although there are several therapeutic agents on the horizon, early diagnosis, and treatment of HoFH remain critical to optimize patient outcomes.

Reciprocal interferences of the left ventricular assist device and the aortic valve competence.

Patients suffering from end-stage heart failure tend to have high mortality rates. With growing numbers of patients progressing into severe heart failure, the shortage of available donors is a growing concern, with less than 10% of patients undergoing cardiac transplantation (CTx). Fortunately, the use of left ventricular assist devices (LVADs), a variant of mechanical circulatory support has been on the rise in recent years. The expansion of LVADs has led them to be incorporated into a variety of clinical settings, based on the goals of therapy for patients ailing from heart failure. However, with an increase in the use of LVADs, there are a host of complications that arise with it. One such complication is the development and progression of aortic regurgitation (AR) which is noted to adversely influence patient outcomes and compromise pump benefits leading to increased morbidity and mortality. The underlying mechanisms are likely multifactorial and involve the aortic root-aortic valve (AV) complex, as well as the LVAD device, patient, and other factors, all of them alter the physiological mechanics of the heart resulting in AV dysfunction. Thus, it is imperative to screen patients before LVAD implantation for AR, as moderate or greater AR requires a concurrent intervention at the time of LVADs implantation. No current strict guidelines were identified in the literature search on how to actively manage and limit the development and/or progression of AR, due to the limited information. However, some recommendations include medical management by targeting fluid overload and arterial blood pressure, along with adjusting the settings of the LVADs device itself. Surgical interventions are to be considered depending on patient factors, goals of care, and the underlying pathology. These interventions include the closure of the AV, replacement of the valve, and percutaneous approach via percutaneous occluding device or transcatheter aortic valve implantation. In the present review, we describe the interaction between AV and LVAD placement, in terms of patient management and prognosis. Also it is provided a comprehensive echocardiographic strategy for the precise assessment of AV regurgitation severity.

Postcardiosurgical Pseudoaneurysm.

Takayasu's arteritis is an autoimmune inflammatory disease of large arteries. We report a case of postcardiac surgery pseudoaneurysm. Anesthetic concerns, high risk related to surgery, necessary anesthetic preparations, and considerations will be mentioned here.

A Case of Status Epilepticus and Transient Stress Cardiomyopathy Associated with Smoking the Synthetic Psychoactive Cannabinoid, UR-144.

BACKGROUND Synthetic cannabinoids have a higher affinity for the cannabinoid receptors CB1 and CB2 than natural cannabinoids. Their use can be associated with cardiovascular disease and neurological complications. A case is reported of status epilepticus and stress cardiomyopathy following the recreational use of the synthetic cannabinoid, UR-144. CASE REPORT A 19-year-old woman presented to the emergency department in status epilepticus after smoking the synthetic cannabinoid known as 'space'. Recurring seizure activity was controlled after three hours. On hospital day 3, the patient developed severe biventricular failure. Cardiac magnetic resonance imaging (MRI) confirmed the diagnosis of stress cardiomyopathy. A comprehensive urine drug screen was performed using gas chromatography-mass spectrometry (GC-MS), which was positive for UR-144, or (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)-methanone, and negative for all other illicit recreational drugs. The patient improved at one week following admission, with a left ventricular ejection fraction (LVEF) of 40%. She was discharged home on hospital day 10. CONCLUSIONS The use of the synthetic cannabinoid, UR-144, may be associated with prolonged status epilepticus and stress cardiomyopathy. Physicians should be aware of these potentially lethal complications associated with the recreational use of this and other illicit synthetic cannabinoids.

Baseline Q waves and time from symptom onset to ST-segment elevation myocardial infarction: insights from PLATO on the influence of sex.

BACKGROUND: The prognostic value of time from symptom onset to reperfusion may be enhanced by the identification of Q waves on the presenting electrocardiogram (ECG) in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated whether the relative prognostic utility of these 2 metrics was altered by sex. METHODS: Q waves in the distribution of the ST-segment elevation on the baseline ECG were evaluated by a blinded core laboratory in 2838 STEMI patients (2163 men and 675 women) from the PLATelet inhibition and patient Outcomes (PLATO) trial who underwent percutaneous coronary intervention (PCI) within 12 hours of symptom onset. RESULTS: Women were older (median 63 vs 57 years), more likely to be diabetic (24.1% vs 15.5%), hypertensive (69.2% vs 50.9%), and a higher Killip class > I (8.6% vs 5.9%), as compared with men. Whereas the Q waves frequency rose progressively over time to ECG in men, this relationship was attenuated in women (P = .057). Q waves on the baseline ECG were associated with a higher excess hazard of 1-year vascular death in men (hazard ratio [HR] 2.03; 95% confidence interval [CI], 1.13-3.72), and a similar trend existed in women (HR 1.97; 95% CI, 0.86-4.51). Women with baseline Q waves tended to have higher risk of 1-year vascular death than men as continuous time from symptom onset to PCI increased (P[interaction] = .182). CONCLUSIONS: These differences in the evolution of baseline Q waves and relationship between time from symptom onset and vascular death in women and men deserve recognition in future studies of STEMI.

Spindle cell sarcoma of the left atrium: an extremely rare and challenging tumour often masquerading as left atrial myxoma.

Spindle-cell sarcoma of the left atrium is an extremely rare diagnosis, with only 4 cases reported in the literature worldwide. We report on a 42-year-old man, who presented to the emergency department with dyspnea and decreased exercise tolerance. A computed tomography chest scan showed a large mass in the left atrium. Echocardiography demonstrated a significant gradient across the mitral valve. The patient had the mass excised in the operating room. He did well postoperatively. Eight months later, a repeat cardiac magnetic resonance imaging scan showed a recurrence. Right pneumonectomy was performed to ensure margins were clear. Although he has done well after surgery, his prognosis remains guarded.