Expert Review of Cardiovascular Therapy

Introduction: Atrial septal defect is the most common congenital heart disease in adults. The secundum defect is the most common anatomical variant. Atrial septal defect usually causes subtle or no symptoms in pediatrics. However, as patients age, the left-to-right shunt increases and more symptoms appear. Atrial septal defect closure is indicated when there is a clinically significant left-to-right shunt, either by echocardiographic data in terms of right-sided dilation, hemodynamic parameters with Qp:Qs ratio over 1.5:1, or the appearance of clinical symptoms. Areas covered: This article reviews secundum atrial septal defects (ASD) with emphasis on device closure outcome in comparison to surgical approaches. The article covers ASD anatomy, pathophysiology, clinical presentation, natural history, imaging evaluation, indications for closure, suitability for transcatheter closure, and outcome of both device closure and surgical closure in the adult patients. Expert opinion: Atrial septal defect closure can be performed either via a transcatheter approach or a surgical approach. The transcatheter approach is preferred worldwide to close secundum ASDs, provided they meet certain anatomical criteria (size and rim sufficiency). The transcatheter approach is more cost-effective, requires a shorter hospital stay, and has similar outcomes with a lower incidence of complications.

Introduction: Dynamic reassessment of stroke and bleeding risks is a cornerstone of patient-centered care in atrial fibrillation (AF) management. Unlike traditional approaches that evaluate these risks only at diagnosis or at initiation of oral anticoagulation, current evidence emphasizes periodic reassessment due to the evolving nature of risks. Areas covered: Stroke and bleeding risks in AF patients are influenced by aging, new comorbidities, and worsening health conditions, requiring updates to management plans to optimize outcomes. Dynamic increases in CHA2DS2-VASc (or the sex-less CHA2DS2-VA) and HAS-BLED scores are associated with heightened risks of stroke and bleeding, underscoring the need for regular reassessment. Addressing modifiable risk factors such as hypertension, renal dysfunction, and concurrent medications is key to improving outcomes. Although several guidelines now recommend risk reassessment at least annually, optimal timing remains unclear. Evidence supports more frequent reassessments for low-risk stroke patients (every 4 months) and high-risk bleeding patients (within 4-6 weeks) to promptly identify changes requiring intervention. Expert opinion: Despite its benefits, challenges remain regarding risk reassessment, including the lack of universally applicable intervals and the complexity of multidisciplinary evaluations. Future advancements in artificial intelligence tools are expected to enhance risk reassessment by enabling more precise, personalized, and dynamic patient management.

Introduction: Refractory angina (RA) is a debilitating condition characterized by persistent angina despite optimized medical therapy and limited options for further revascularization, leading to diminished quality of life and increased healthcare utilization. The RA patient population is rapidly expanding with significant unmet needs. Specialty clinics should be developed to focus on the long-term efficacy and safety of clinically available and novel treatment strategies, emphasizing quality of life. Areas covered: Patient-focused Comprehensive Angina Relief (CARE) clinics can enhance care and outcomes by providing individualized management for complex RA. This review summarizes peer-reviewed articles from PubMed and trial data from ClinicalTrials.gov. We discuss the epidemiology and pathophysiology of RA, introduce standardized tools for evaluating angina and psychosocial factors, and address symptom management. We also review treatment options such as risk factor modification, medication, and complex revascularization. Additionally, we explore emerging therapies, including coronary sinus occlusion, regenerative therapy, and neuromodulation for 'no-option' RA. Expert opinion: In the next five years, patients with refractory chest pain with or without coronary artery disease will increasingly be referred to specialty clinics for follow-up. Conducting more randomized control clinical trials with larger population subsets will bring novel therapies to the forefront.

Introduction: Tricuspid regurgitation (TR) is a prevalent condition and is independently associated with high morbidity and mortality rates. Despite its prognostic impact, TR remains undertreated, with patients often referred at late stages when medical therapy is ineffective and surgical intervention high risk. Emerging transcatheter therapies offer a promising alternative for safer and effective management of this elderly patient population with numerous comorbidities. Areas covered: This review highlights recent advances in treatment strategies and future directions for addressing significant TR. The literature search was conducted across the PubMed, Embase, Scopus, and Google Scholar databases. A structured search strategy was developed using 'tricuspid regurgitation' and 'management' or 'treatment' or 'therapy' and 'surgery' or 'tricuspid valve repair' or 'tricuspid valve replacement' or 'transcatheter tricuspid intervention' as MeSH terms and keywords. Selected articles from 2017 to present were critically analyzed for strengths, limitations, and gaps in evidence. Expert opinion: Enhancing disease awareness, the involvement of multidisciplinary Heart Team and intervening earlier are critical priorities for TR therapies to prevent treatment futility. Improved device designs, more performant imaging techniques, and dedicated research endpoints will help optimizing the management of TR.

Introduction: Left atrial appendage occlusion (LAAO) represents a strategy to minimize thromboembolic risk in atrial fibrillation (AF) patients. However, LAAO carries some risks of periprocedural bleeding, device embolization, peri-device leaks or device-related thrombosis; the latter is due to direct blood contact with the device, justifying and represents the rationale behind antithrombotic therapy following LAAO. Areas covered: A comprehensive literature search (PubMed, Web of Science, Cochrane) has been performed up to November 2024. Antithrombotic drugs after LAAO include vitamin K antagonists (VKA), direct oral anticoagulants (DOAC), antiplatelet drugs, and their combinations. Initially, high-intensity regimens were implemented, while current strategies prioritize simplified approaches to promote device healing without increasing the bleeding risk. The aims of our review were to define the rationale and implications for post-LAAO antithrombotic therapy and provide an overview of current evidence on various antithrombotic regimens. Expert opinion: The optimal post-LAAO antithrombotic regimen remains controversial, highlighting the need for randomized trials on this topic. Current data suggest that DOACs have the lowest probability of thromboembolic events and major bleeding, while DAPT may be preferred in patients who do not tolerate OAC; finally, single antiplatelet therapy or no antithrombotic therapy are alternative options for patients at high bleeding risk.

Objectives: To perform a systematic review to compare the efficacy and safety of transcatheter pulmonary valve replacement (TPVR) and surgical pulmonary valve replacement (SPVR) in managing pulmonary valve dysfunction in Tetralogy of Fallot (TOF) patients. Methods: This review investigates through three different databases for randomized control trials or observational studies evaluating TOF patients who underwent TPVR or SPVR until November 2024. The outcomes of interest were hemodynamic improvement, reduction in pulmonary regurgitation or stenosis, complications, quality of life, and long-term outcomes. Results: Four retrospective studies (1919 procedures) were analyzed. TPVR was non-inferior to SPVR, with a comparable safety profile. The durability of bioprosthetic valves was similar between TPVR and SPVR (HR: 0.97, 95% CI: 0.55-1.73; p = 0.93) and was influenced by patients' age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; p = 0.02) and true inner valve diameter . Conclusions: TPVR is a safe and less-invasive alternative to SPVR with comparable efficacy in reducing pulmonary regurgitation. Complication rates are similar and valve durability is primarily age- and valve size-dependent. Although further research on long term outcomes is needed, TPVR may be integrated into routine practices, offering a viable alternative for high-risk TOF patients. Registration: This systematic review was registered on the international prospective register of systematic reviews (PROSPERO; #CRD42024615871).

Introduction: Invasive management of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) should be considered regardless of age, but a key challenge is deciding which patients are most likely to benefit from an invasive approach in the older population. In addition to assessment of the clinical signs and symptoms, a holistic assessment of geriatric syndromes such as frailty, multimorbidity and cognitive impairment is of increasing importance. Recent trials have validated the roles of physiological assessment and intracoronary imaging to guide revascularisation. Areas covered: This review focuses on the comparison between invasive and conservative management in the older population with NSTE-ACS, the clinical characteristics of the older population with NSTE-ACS, and the role of physiological assessment and intracoronary imaging to guide revascularisation in this cohort. Expert opinion: Invasive management in the older population with NSTE-ACS may not improve mortality but reduces the risk of non-fatal myocardial infarction and repeat revascularisation. Decisions surrounding invasive versus conservative management should be individualized to each patient, depending on patient preference, clinical features, comorbidities and frailty. In patients where invasive management is indicated, a combination of physiological assessment and intracoronary imaging is likely to improve revascularisation outcomes, especially in the context of complex anatomical characteristics like multivessel disease.

Background: Late adverse myocardial remodeling after ST elevation myocardial infarction (STEMI) is strongly associated with cardiac death. Global Longitudinal strain (GLS) and circumferential diastolic strain rate (CDSR) derived cardiovascular magnetic resonance imaging (CMRI) is a powerful predictor of late myocardial remodeling. However, the Impella's effects on CMRI after STEMI are not fully understood. Research design and methods: We retrospectively compared the CMRI in the acute (18 [14-22] vs. 14 [6-22] days, p = 0.43) and chronic phases (118 [102-242] vs. 117 [101-202] days, p = 1.0) after anterior STEMI. Results: Five patients received Impella before percutaneous coronary intervention (PCI), and seven underwent intra-aortic balloon pumping (IABP). There were no significant differences in the peak creatine kinase levels (2595 [2069 -12,932] vs. 4372 [2941-5601] IU/L, p = 0.76) and LVEF upon admission (51 ± 11 vs. 50 ± 9%, p = 1.0). The Impella group had significantly better acute CMRI-derived LVEF (49 ± 10 vs. 35 ± 7%, p = 0.02) and CDSR (0.9 ± 0.2 vs. 0.5 ± 0.3 s- 1, p = 0.018). In the chronic phase, the CMRI-derived LVEF and GLS were significantly higher in the Impella group (54 ± 9 vs. 39 ± 5%, p = 0.01; -9.9 ± 1.3 vs. -6.5 ± 2.2%, p = 0.01). Conclusions: The Impella implantation led to better LVEF and CDSR in the acute phase than IABP and better maintenance of both the LVEF and GLS through the chronic phase.

Objective: To analyze the cost-effectiveness of apixaban in the prevention of stroke in adult patients with non-valvular atrial fibrillation (NVAF), compared to other direct-acting oral anticoagulants (dabigatran, rivaroxaban, edoxaban) and the vitamin K antagonist acenocoumarol, based on data on effectiveness in clinical practice in Spain obtained in the FANTASIIA study. Research design and methods: A probabilistic Markov economic model (second-order Monte Carlo simulation) was performed to analyze the costs and utilities (quality-adjusted life years, QALYs) associated with the compared treatments, according to the different probabilities of stroke, major bleeding and death observed in FANTASIIA. Results: The cost per QALY gained in the patient treated with apixaban versus comparators ranged from €2,919 to €7,462. The probability of apixaban being cost-effective ranges from 91.1% (vs dabigatran 150 mg), 97.8% (vs dabigatran 110 mg), and 100% (vs. rivaroxaban, edoxaban, and acenocoumarol). Conclusions: Based on the results of the FANTASIIA study, apixaban is a cost-effective treatment (below a willingness to pay of €25,000 per QALY gained) compared to dabigatran, rivaroxaban, edoxaban, and acenocoumarol in treating patients with NVAF.

Background: We present an analysis of cardiovascular-related deaths specific to hematological cancer patients in the United States from 1999 to 2020, examining trends in relation to age, gender, and type of hematological cancer. Research design and methods: Utilizing the Multiple Cause of Death databases, our research included 88,146 decedents with cardiovascular primary cause of death and with hematologic disease. We determined the percentage of cardiovascular deaths associated with each disease category. Furthermore, we developed age-adjusted mortality rates, categorizing them based on sex, age, race, Latino origin, and the type of hematological cancer. Results: Between 1999 and 2020, there was a decreasing temporal trend in overall cardiovascular mortality for lymphoma, leukemia and multiple myeloma (-38.8% -31.8% & -29.4%). The most common cardiovascular mortality cause in the hematological malignancy population was ischemic heart disease, followed by cerebrovascular disease (53.4%, 20.2%). African American, Asian, and White patients showed decreasing for overall CV death for all hematological malignancies, with African American subgroups showing the lowest mortality reduction over time (AAMR: -26.8%, -41.2%, -33.3%). However, hypertension mortality increased for most racial groups. Conclusions: Over the last 2 decades, the rate of cardiovascular mortality amongst patients with underlying hematological malignancy has decreased.

Introduction: The pathophysiology of cardiovascular diseases encompasses a complex interplay of genetic and environmental risk factors. Even if traditional risk factors are treated to target, there remains a residual risk. Areas covered: This manuscript reviews the potential role of gut microbiota in the development of cardiovascular disease, and as potential target. A systematic search was conducted until 30 October 2024 on PubMed (MEDLINE), using the MeSH terms [Gut microbiota] + [Dysbiosis] + [Cardiovascular] + [TMAO] + [bile acids] + [short-chain fatty acids]. Expert opinion: The term dysbiosis implies changes in equilibrium, with modifications in the composition and functionality of microbiota and a series of additional factors: reduced diversity and uniformity of microorganisms; reduced short-chain fatty acid-producing bacteria; increased gut permeability; release of metabolites, such as trimethylamine N-oxide, betaine, phenylalanine, tryptophan-kynurenine, phenylacetylglutamine, and lipopolysaccharides; and reduced secondary bile acid excretion, leading to inflammation, oxidative stress, and endothelial dysfunction and facilitating the onset of pathological conditions, including obesity, hypertension, diabetes, atherosclerosis, and heart failure. Attempts to restore gut microbiota balance through different interventions, mainly changes in diet, have been shown to positively affect individual components and metabolites and reduce the risk of cardiovascular disease. In addition, probiotics and prebiotics are potentially useful. Fecal microbiota transplantation is a promising therapy.

Introduction: People living with HIV (PLHIV) are at higher risk of cardiovascular disease (CVD), and dyslipidemia is a prevalent comorbidity that requires effective treatment. Limitations for the use of statins such as drug interactions and adverse effects highlight the need for alternative therapies. Areas covered: This review evaluates the role of PCSK9 inhibitors in reducing cardiovascular risk in PLHIV with dyslipidemia. We analyzed studies available on PUBMED, using keywords HIV, dyslipidemia, PCSK9 inhibitors, and statin intolerance. We discuss the mechanisms underlying increased cardiovascular risk, limitations of statins, including a recent study using PCSK9 inhibitors. Evolocumab significantly reduced LDL-C levels by 56.9% in PLHIV, with 72.5% of patients achieving ≥50% LDL-C reduction. The trial confirmed the drug's safety. Additionally, PCSK9 inhibitors demonstrated reductions in lipoprotein(a) and inflammatory markers. Expert opinion: PCSK9i present a promising option for lipid management in PLHIV, especially in statin-intolerant individuals or those with residual risk despite statin therapy. Additional non-statin therapies targeting adverse lipid profiles, including low HDL-C, high triglycerides, and lipoprotein(a), are under development. Combined with advancements in antisense oligonucleotides (ASOs) and siRNA technologies, they hold promise for transforming the treatment of dyslipidemia and cardiovascular disease in PLHIV.

Introduction: Out-of-hospital cardiac arrest (OHCA) is a critical condition associated with high mortality rates and neurological impairment among survivors. In comatose OHCA patients who achieve return of spontaneous circulation, early risk stratification is important to inform treatment pathways and potentially improve outcomes. A range of prognostic tools have been developed to predict survival and neurological recovery. Each tool incorporates a unique combination of clinical, biochemical and physiological markers. Areas covered: This review article evaluates the required clinical data, predictive performances and practical applicability of major risk scores. A literature review was conducted in PubMed and Embase for studies published between January 2000 and October 2024. The review emphasizes the variability in discriminative power among the selected scores, with some models offering high sensitivity and specificity in outcome prediction, while others prioritize simplicity and accessibility. Expert opinion: Despite the advancements of these tools, limitations persist in data dependency and the clinical adaptability, highlighting areas for future improvement. Integrating artificial intelligence and real-time analytics could enhance predictive accuracy, offering dynamic prognostic capabilities that adapt to individual patient trajectories. This evolution must be grounded in ethical considerations to ensure predictive technologies complement rather than replace clinical judgment, balancing technology's potential with the complexities of individualized patient care.

Background: Stroke is a potential complication of Transcatheter Aortic Valve Replacement (TAVR). Recent trials evaluating Cerebral Embolic Protection Systems (CEPS) to reduce the incidence of stroke after TAVR have been conflicting. Methods: Multiple databases were searched for studies comparing TAVR with or without CEPS and that reported on the primary outcome of periprocedural stroke. Two authors individually screened the titles, the abstracts and the full texts using Covidence. Risk of bias was assessed using Cochrane's ROB-2 and ROBINS-I tools. Results: A total of 15 studies (3 randomized controlled trials, 7 national registries, and 5 cohort studies) met the eligibility criteria and were included in our review. CEPS was associated with lower rates of periprocedural stroke [OR 0.71 (95% CI 0.55, 0.93) p = 0.012], as well as lower rates of mortality [OR 0.60 (95% CI 0.49, 0.74) p < 0.001]. There was no significant difference between the two groups in the incidence of acute kidney injury [OR 0.91 (95% CI 0.82, 1.01) p = 0.087], major vascular complications [OR 0.97 (95% CI 0.83, 1.14) p = 0.734], and major life-threatening bleeding [OR 0.89 (95% CI 0.73, 1.07) p = 0.222]. Conclusions: Our findings suggest that the use of CEPS in TAVR is associated with a lower risk of periprocedural stroke and mortality. Registration: The PROSPERO identification number is CRD42022374055.

Background: This study aimed to evaluate the effects of hydroxychloroquine on cardiac functions and left ventricular mass in patients with childhood-onset systemic lupus erythematosus (cSLE). Research design and methods: Fifty patients with cSLE undergoing treatment with hydroxychloroquine underwent echocardiographic evaluation. All patients exhibited negative disease activity markers and were clinically in remission. Results: The median duration of hydroxychloroquine exposure was 7.1 (5.2-9.5) years, with a median cumulative dose of 784.8 (509.5-3437.6) grams. No correlation was identified between the parameters of left ventricular ejection fraction, left ventricular mass index and geometry, and cumulative hydroxychloroquine dose (p = 0.245, p = 0.094, p = 0.146, respectively). Furthermore, no significant correlation was identified between the cumulative dose of hydroxychloroquine and diastolic cardiac parameters (all p > 0.05). A comparison of the patients who received a cumulative dose of hydroxychloroquine below the median dose (the low-dose group) with those who received a higher dose (the high-dose group) revealed no significant differences in the echocardiographic parameters (all p > 0.05). Conclusions: The findings of this study indicate that chronic hydroxychloroquine use in patients with cSLE does not result in adverse changes in left ventricular mass or impairment of cardiac functions. However, these patients should undergo regular evaluation to monitor for the potential development of cardiotoxicity.

Introduction: Cardiac Resynchronization Therapy (CRT) is an effective treatment for heart failure (HF) in approximately two-thirds of recipients, with a third remaining CRT 'non-responders.' There is an increasing body of evidence exploring the reasons behind non-response, as well as ways to preempt or counteract it. Areas covered: This review will examine the most recent evidence regarding optimizing outcomes from CRT, as well as explore whether traditional CRT indeed remains the best first-line therapy for electrical resynchronization in HF. We will start by discussing methods of preempting non-response, such as refining patient selection and procedural technique, before reviewing how responses can be optimized post-implantation. For the purpose of this review, evidence was gathered from electronic literature searches (via PubMed and GoogleScholar), with a particular focus on primary evidence published in the last 5 years. Expert opinion: Ever-expanding research in the field of device therapy has armed physicians with more tools than ever to treat dyssynchronous HF. Newer developments, such as artificial intelligence (AI) guided device programming and conduction system pacing (CSP) are particularly exciting, and we will discuss how they could eventually lead to truly personalized care by maximizing outcomes from CRT.

Introduction: Hypertension is very common and a major risk factor for cardiovascular disease, heart failure, chronic kidney disease, strokes, and death. However, at present only 14% of patients of developing countries have their blood pressure (BP) well controlled. The causes for the failure to control the BP are multiple and one of them could be the formulation of antihypertensive drugs. Areas covered: The recent development of nanotechnology by incorporating the drugs into nanoparticles is a new promising field of nanomedicine and preliminary studies have shown this nanoformulation to be more effective in the treatment of hypertension than the existing drug formulations. Another recent development is the nanoformulation of genes used for the treatment of hypertension and cardiovascular diseases. For current information, a Medline search was conducted between 2017 and 2024 and 36 pertinent papers were selected. Expert opinion: The nanoformulations of drugs help achieve better drug concentrations, improve drug stability, low solubility, short half life, oral bioavailability, narrow therapeutic index, and poor pharmacokinetic and pharmacodynamic profiles, and decrease the adverse effects of antihypertensive drugs. Also, the nanoformulation of genes for the treatment of hypertension has been shown in preliminary studies to be effective, but more research is needed.