Aro Daniela Arockiam

Cystic fibrosis (CF) has undergone a remarkable transformation from a fatal childhood disease to a chronic adult condition, with a median predicted survival now exceeding 50 years following the introduction of highly effective CFTR modulator therapy (HEMT). This demographic shift has unmasked cardiovascular complications that were previously unrecognized due to premature mortality. In a multinational propensity-matched cohort, CF conferred a 65% higher risk of major adverse cardiac events (MACEs), including myocardial infarction, heart failure, and atrial fibrillation, versus matched controls (Frost et al., HR 1.65). In a separate Canadian population-based cohort, cardiovascular disease occurred at 2.9 times the rate of the general population and at least 20 years earlier (Arya et al., RR 2.9). Cardiac involvement extends beyond the traditional paradigm of cor pulmonale. CFTR is expressed in cardiomyocytes, vascular endothelium, and smooth muscle, where its dysfunction disrupts ion homeostasis, impairs nitric oxide-dependent vasodilation, and promotes oxidative stress. Clinically, these mechanisms manifest as biventricular dysfunction detectable by strain echocardiography and cardiac MRI even when ejection fraction is preserved, diffuse myocardial fibrosis, endothelial dysfunction and accelerated arterial stiffness from childhood, increased arrhythmia susceptibility, and, in a single-center cohort, an unexpectedly high prevalence of pericardial calcification (18%) on chest CT that awaits independent replication. Paradoxically, while HEMT has dramatically improved pulmonary outcomes, it introduces new cardiovascular considerations including hypertension, dyslipidemia, and obesity, and cross-sectional data in modulator-treated cohorts show persistent cardiac abnormalities, though whether these predate treatment or would differ without it is unknown. This review synthesizes the genetic, molecular, and clinical dimensions of cardiovascular disease in CF; distinguishes direct CFTR-mediated cardiac effects from indirect consequences of chronic lung disease; examines vascular, electrophysiological, valvular, and pericardial manifestations; and discusses management implications including CFTR modulator therapy, exercise, nutritional paradigm shifts, and transplantation considerations.

Coronary artery aneurysms (CAA) present variably and require multimodal imaging—catheterization, CTCA, stress echocardiography among others—for diagnosis. Management, individualized per patient, includes medical, percutaneous, or surgical approaches. A successful surgical case showed improved cardiac function and symptoms, highlighting the vital role of advanced imaging in guiding treatment.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but carry a risk of immune‐related adverse events, reported in 15% to 90% of the patients. ICI‐associated pericardial and myocardial disease has been increasingly recognized, yet data on outcomes remain limited. We aimed to use a large real‐world database to investigate the short‐ and long‐term outcomes of ICI‐associated pericarditis, myocarditis, and myopericarditis versus the non‐ICI cases. Methods: We conducted a retrospective analysis using the TriNetX database to identify patients >18 years old on ICI and diagnosed with pericarditis, myocarditis, or myopericarditis within 1 year of initiation of therapy. The primary outcome assessed was all‐cause mortality, tamponade, constrictive pericarditis, and need for pericardiocentesis at 90‐day, 1‐year, and 5‐year follow‐up. Results: A total of 3661, 226, and 46 patients were identified in matched cohorts of ICI‐induced pericarditis, myocarditis, and myopericarditis, respectively. One‐ and 5‐year mortality was greater for pericarditis (44.3% versus 37.3%; 54.3% versus 46.9%), myocarditis (38.9% versus 20.8%; 47.8% versus 34.3%), and myopericarditis (56.5% versus 28.3%; 63.0% versus 28.3%; all P ≤0.002). A multivariable Cox model showed increased ICI‐related mortality for pericarditis 1‐year hazard ratio [HR], 1.20 (95% CI, 1.12–1.29), 5‐year HR, 1.26 (95% CI, 1.18–1.35), myocarditis 90‐day HR, 1.82 (95% CI, 1.21–2.73), 1‐year HR, 2.04 (95% CI, 1.43–2.91), 5‐year HR, 1.64 (95% CI, 1.26–2.61), and myopericarditis 1‐year HR, 2.24 (95% CI, 1.15–4.37), and 5‐year HR, 2.78 (95% CI, 1.44–5.36), all with P <0.001. Conclusion: Among 3661, 226, and 46 patients with ICI‐associated pericarditis, myocarditis, and myopericarditis, respectively, we demonstrated an increased risk of all‐cause mortality as compared with the respective non‐ICI population.

Evidence is accumulating that shows spontaneous coronary artery dissection (SCAD) as a recognized cause of acute coronary syndrome (ACS), disproportionately affecting younger people and women. Moreover, despite continuing progress, the understanding of the pathophysiology, diagnosis, and management of SCAD remains limited. SCAD, by definition, is a non-atherosclerotic formation of an intramural hematoma or intimal tear, yet current diagnostic criteria and management are derived from atherosclerotic ACS guidelines. This review encompasses the current understanding of the condition, including risk factors, diagnostic and imaging modalities available for detection, differentials to be considered, associations with other comorbidities, prognostic factors, and management options for both the short and long term, encompassing both medical and interventional therapies. Meanwhile, a lack of research in key populations, such as non-pregnant women, postmenopausal women, and men, prevents the generalizability of these findings and has been highlighted. However, by identifying and conceptualizing existing evidence, this review aims to provide direction to future research.

Cardiovascular complications are increasingly recognised as a major driver of morbidity and early mortality in patients with sickle cell disease (SCD), yet they remain underdiagnosed and underappreciated. This contemporary review synthesises current knowledge across a spectrum of cardiovascular manifestations—including myocardial dysfunction, pulmonary hypertension, cardiac iron overload, arrhythmias, myocardial infarction, stroke and sudden death—with emphasis on their unique pathophysiological mechanisms in SCD. We highlight emerging diagnostic tools such as cardiac magnetic resonance with T2* mapping and extracellular volume sequences, speckle-tracking echocardiography and invasive exercise testing, which can revealing a distinct phenotype combining restrictive cardiomyopathy and high-output heart failure. Practical algorithms for risk stratification and disease monitoring are presented alongside evidence-based and SCD-specific management approaches, including the role of hydroxyurea, transfusions, anticoagulation and gene therapy. By integrating multimodality imaging, updated guideline recommendations and recent clinical insights, this review provides a comprehensive resource to support early recognition, personalised therapy and improved cardiovascular outcomes in SCD.

Cardiac iron overload is a rare but important adverse consequence of systemic iron overload, marked by the abnormal accumulation of iron in the myocardium. It is most typically caused by hereditary hemochromatosis (mutations in the HFE gene) or secondary iron overload conditions, such as transfusion-dependent anemias. Excess iron in the myocardium causes oxidative stress, cardiomyocyte damage, and progressive fibrosis, ultimately leading to cardiomyopathy. Clinical manifestations are diverse and may include heart failure, arrhythmias, and restrictive or dilated cardiomyopathy. Given the worsened prognosis with cardiac involvement, timely diagnosis and management are essential to improve clinical outcomes. This review provides a contemporary overview of the cardiovascular complications associated with iron overload, including clinical manifestations, diagnostic approaches, and treatment options.

BACKGROUND: Aortic valve calcium score (AVCa) measured on noncontrast computed tomography (CT) is well-established for grading aortic stenosis (AS) severity. However, thresholds for AVCa measured on contrast CT remain uncertain. We evaluated correlations, associated factors, and severity thresholds of AVCa measured on contrast CT against transthoracic echocardiography (TTE) measures of AS. METHODS: Patients with native AS undergoing transcatheter aortic valve replacement evaluation from 2019 to 2020 who underwent TTE and contrast-enhanced CT were retrospectively studied (n=1035, age 79±9 years, 429 (41.5%) women, 906 (87.5%) severe and 129 (12.5%) moderate AS by TTE). AVCa was measured using the modified Agatston method with the minimum threshold of 4 SD above the mean ascending aorta blood pool Hounsfield units. Receiver-operating characteristics analysis and Youden index were used to define sex-specific optimal AVCa thresholds for identifying severe AS defined by TTE (aortic valve area by continuity equation ≤1.0 cm ² ) in the derivation cohort and assessed when applied to the validation cohort. RESULTS: Mean aortic valve area on TTE was 0.79±0.21 cm ² , while mean AVCa score, volume, and mass were 2152±1102 modified AU, 1853±1592 mm ³ , and 673±485 mg, respectively. Multivariable linear regression identified women to be associated with lower AVCa (β-coefficient, −358), while chronic kidney disease was associated with a higher AVCa (β-coefficient, 171). Optimal severe AS thresholds of ≥1840 modified AU for men and ≥1430 modified AU for women were determined, with area under curve (95% CIs) and sensitivities/specificities of 0.809 (0.749–0.869, 71.3%, 82.2%) for men and 0.822 (0.751–0.892), 73.4%/78.9% for women in the derivation cohort, and 0.830 (0.786–0.875), 75.9%/87.5% for men and 0.780 (0.670–0.890), 77.5%/71.4% for women in the validation cohort. CONCLUSIONS: AVCa by contrast CT is a useful tool for identifying severe AS by TTE, with sex-specific thresholds for severe AS identified. Further studies are necessary to externally validate our findings and evaluate their prognostic significance.

Aortic regurgitation (AR) is a valvular heart disease characterized by the pathological backflow of blood from the aorta into the left ventricle during diastole, causing left ventricular pressure and volume overload. This results in dilation and enlargement of the left ventricle, causing left ventricular hypertrophy and, ultimately, left ventricular dysfunction. AR has a wide range of causes, which include congenital, acquired, and genetic diseases. Therefore, AR may present as an acute condition causing hemodynamic compromise or as a chronic condition with a long asymptomatic phase, which could progress to heart failure (HF). The clinical profile and the disease trajectory depend on the age, sex, and the type of underlying AR pathology. Noninvasive cardiac multimodality imaging (cMMI) has been integral in the serial monitoring and management of AR. Meanwhile, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are mainly utilized as the first-line diagnosis and monitoring options for AR. Furthermore, cardiac magnetic resonance imaging (CMR) is useful in assessing regurgitant volume and the degree of myocardial remodeling. Cardiac computed tomography (CT) is another second-line imaging modality used to evaluate anatomy, particularly for surgical planning. These modalities allow a systematic assessment of AR disease severity and therapeutic decision-making. Surgical aortic valve replacement (SAVR) is the recommended modality for treating severe symptomatic AR. Meanwhile, transcatheter aortic valve replacement (TAVR) may be a potential interventional option for patients at elevated surgical risk; however, the evidence remains limited to patients with mixed aortic valvular disease. Therefore, new research is currently being performed in artificial intelligence and four-dimensional imaging to optimize the diagnostic accuracy of imaging techniques and identify patients who would benefit from early intervention, thus improving outcomes. The primary objective of this review is to explore the different indications, advantages, and disadvantages of cMMI in the diagnosis, follow-up, and treatment of severe AR, highlighting how cMMI can be utilized in optimizing clinical decision-making and patient outcomes.

Isolated tricuspid regurgitation (TR) represents a significant yet understudied cardiac condition, primarily arising from structural valve anomalies or secondary to right ventricular (RV) dysfunction. This thesis reviews the pathophysiology, clinical picture, and evolving management strategies for isolated TR, focusing on medical and surgical interventions and emerging transcatheter therapies. Employing a comprehensive literature review and retrospective analyses, we delve into the etiological factors, diagnostic challenges, and treatment outcomes associated with this condition. Notably, we explore the prognostic implications of isolated TR following mitral valve surgery and the efficacy of various treatment modalities in improving patient survival and quality of life.

Bicuspid aortic valve (BAV) is a common congenital cardiac anomaly, characterized by the presence of two functional aortic valve leaflets instead of the usual three. It affects approximately 1 – 2% of the population and is often associated with other cardiovascular complications, including aortic stenosis, aortic regurgitation, and aortic root dilation. BAV can present with a wide range of clinical manifestations, from asymptomatic individuals to those with severe aortic valve dysfunction or aortic dissection. The diagnosis of BAV is commonly established through non-invasive imaging techniques such as transthoracic and transesophageal echocardiography, with advanced modalities, such as computed tomography and magnetic resonance imaging providing superior delineation of valve morphology, aortic root measurements, and associated pathology. Management of BAV is multifaceted and depends on the severity of valvular and aortic involvement. Lifelong surveillance is often necessary, with serial imaging to monitor disease progression. Surgical intervention is indicated for patients with severe valve dysfunction, symptomatic disease, or aortic aneurysm exceeding established threshold diameters. Common procedures include aortic valve replacement (AVR) and composite graft repair, such as the Bentall or valve-sparing David procedure. Transcatheter AVR has also emerged as a less invasive alternative to surgical valve replacement within this patient population, with its indications expanding significantly in recent years due to growing interest and advancements in the field. Despite substantial progress in diagnostic and therapeutic strategies, BAV poses clinical challenges due to its heterogeneous presentation, genetic underpinnings, and the requirement for tailored management approaches.