Iatrogenic atrial septal defects in structural heart interventions: Opening the Pandora's box.

In the modern era of structural heart interventions, the total number of transseptal procedures is growing exponentially, thus increasing the rate and need for management of iatrogenic atrial septal defects (iASDs). To date, there are no official guidelines on the assessment and management of iASDs, due to inconclusive evidence on whether patients benefit more from the percutaneous closure of iASD than from conservative management and vigorous follow-up. Despite the abundance of observational studies on iASDs, there is still a lack of randomized studies. Evidence so far show that percutaneous closure is no superior over conservative treatment in patients with iASDs, however, it has been demonstrated that patients with spontaneous closure of iASDs experience less heart failure (HF) hospitalizations. On the other hand, researchers have investigated the beneficial nature of interatrial shunt therapy in patients with HFpEF and, more recently, with HFrEF, due to the presumed hemodynamic benefits. Herein, we provide an updated review of relevant literature, focusing on iASD persistence rates, predicting factors for their persistence, and clinical outcomes of iASD persistence, to summarize available evidence and discuss future directions in the field.

Transvenous extraction of permanent pacemaker and defibrillator leads: Reduced procedural complexity and higher procedural success rates in patients with infective versus noninfective indications.

INTRODUCTION: Transvenous lead extraction (TLE) is critical in the long-term management of patients with cardiac implanted electronic devices (CIEDs). The aim of the study is to evaluate the outcomes of TLE and to investigate the impact of infection. METHODS AND RESULTS: Data of patients undergoing extraction of permanent pacemaker and defibrillator leads during October 2014-September 2019 were prospectively analyzed. Overall, 242 consecutive patients (aged 71.0 ± 14.0 years, 31.4% female), underwent an equal number of TLE operations for the removal of 516 leads. Infection was the commonest indication (n = 201, 83.1%). Mean implant-to-extraction duration was 7.6 ± 5.4 years. Complete procedural success was recorded in 96.1%, and clinical procedural success was achieved in 97.1% of attempted lead extractions. Major complications occurred in two (0.8%) and minor complications in seven (2.9%) patients. Leads were removed exclusively by using locking stylets in 65.7% of the cases. In the subgroup of noninfective patients, advanced extraction tools were more frequently required compared to patients with CIED infections, to extract leads (success only with locking stylet: 55.8% vs. 67.8%, p = .032). In addition, patients without infection demonstrated lower complete procedural success rates (90.7% vs. 97.2%, p = .004), higher major complication rates (2.4% vs. 0.5%, p = .31) and longer procedural times (136 ± 13 vs. 111 ± 15 min, p = .001). CONCLUSIONS: Our data demonstrate high procedural efficacy and safety and indicate that in patients with noninfective indications, the procedure is more demanding, thus supporting the hypothesis that leads infection dissolves and/or prohibits the formation of fibrotic adherences.

Long-term endothelial dysfunction after trans-radial catheterization: A meta-analytic approach.

BACKGROUND: Following cardiac catheterization using radial artery (RA) access, persistent endothelial dysfunction may limit the use of RA as a conduit during coronary artery bypass graft (CABG) surgery. We reviewed published literature to investigate the effects of transradial coronary catheterization on RA endothelial function. METHODS: We searched PubMed from inception to April 2017 for published studies assessing RA endothelial function late (≥1 month) after coronary catheterization. A total of 12 eligible published studies (n = 490 patients) were included in the final quantitative synthesis. Statistical heterogeneity among studies was assessed by the I2 . A random effects model was used to calculate the pooled estimate for standardized mean difference (SMD). Meta-regression analysis was used to explore predictors of change in RA endothelial function following catheterization. RESULTS: In all studies, a significant reduction in endothelium dependent response was observed post-catheterization (SMD = -0.53, 95% confidence interval [CI]: -0.93 to -0.13, P = 0.01) and a marginal, non-significant, reduction in endothelium independent response (SMD = -0.38, 95%CI: -0.77, 0.01, P < 0.059). In controlled studies, using the contralateral RA as a control, a significant impairment in endothelial function was confirmed (SMD = -6.26, 95%CI: -9.71 to -2.81, P < 0.0001), while the change in endothelium-independent response was not significant (SMD = -4.46, 95%CI: -13.3 to 4.37, P = 0.32). In meta-regression analysis male gender (z = 2.36, P = 0.018) and increasing time following catheterization (z = 2.62, P = 0.009) were associated with less RA endothelial dysfunction. CONCLUSIONS: Transradial catheterization impairs endothelium dependent vasodilatory properties of the cannulated RA, which do not recover even several months post-catheterization. Non-recovery of vasomotor function of cannulated RAs may limit their use as arterial grafts during CABG surgery.

Beneficial effects of low-dose aspirin on aortic stiffness in hypertensive patients.

While treatment with low-dose aspirin has been established as a therapeutic tool for secondary prevention, the role of aspirin on primary prevention remains controversial. Aortic stiffness and wave reflections are independent predictors of cardiovascular events. The aim of the present study was to investigate the effect of low-dose aspirin on aortic stiffness and wave reflections in hypertensive patients. We studied 30 patients with grade I hypertension. Fifteen patients were treated with 160 mg of aspirin and 15 patients with placebo. Aortic stiffness and wave reflections were assessed by measuring carotid-femoral pulse wave velocity (PWV) and heart rate-adjusted augmentation index (AIx75), respectively. All measurements were conducted at baseline and 2 weeks after treatment. In the aspirin group, there was a significant reduction in PWV compared to the placebo group (from 8.9±1.5 to 8.5±1.6 m/s for the aspirin group vs from 8.6±1.4 to 8.7±1.6 m/s for the placebo group, net change: -0.5 m/s; p=0.02). AIx75 showed a marginal decrease (from 28.0±5.4 to 26.2±5.0% for the aspirin group vs from 31.2±9.7 to 30.6±9.2% for the placebo group, net change: -1.2%; p=0.06). In conclusion, a 2-week course of aspirin administration has a favorable effect on aortic stiffness and, to a lesser extent, on wave reflections in hypertensive patients. Whether the reduction in arterial stiffness is translated to fewer cardiovascular events needs to be confirmed by future prospective studies.

Intravascular ultrasound-guided, lithotrispy facilitated angioplasty for treating a heavily calcified renal artery stenosis.

A 63-year-old woman with uncontrolled hypertension despite taking 5 antihypertensive medications was referred for percutaneous renal artery intervention.

Transcatheter Structural Heart Disease Interventions and Concomitant Left Atrial Appendage Occlusion: A State-of-the-Art Review.

Atrial fibrillation (AF) is the most common arrhythmia in patients with valvular heart disease, and it can be associated with adverse patient outcomes. However, the need of anticoagulation to counterbalance AF-associated stroke risk may further lead to suboptimal outcomes via increasing bleeding events, especially in high-risk individuals. Currently, the option to perform a concomitant to the index procedure for limiting stroke risk is emerging, in accordance to usual practice in cardiac surgery. In specific, as the vast majority of thrombi occur in the left atrial appendage, left atrial appendage occlusion (LAAO) is an established procedure for preventing ischemic stroke in patients with AF, while limiting anticoagulation-related bleeding events. Thus, the concept of combining an index procedure for a structural heart disease (SHD) with LAAO seems promising for preventing future stroke events. A combined procedure has been described in aortic stenosis (TAVI+LAAO), mitral regurgitation (TEER+LAAO) and atrial septal defects (PFO/ASD+LAAO). Evidence shows that a combined procedure can be safely performed in a "one-stop shop" fashion, without increased rates of procedural adverse events, with the potential to limit bleeding risk and provide prophylaxis against stroke events. Thus, this review is going to analyze indications and clinical evidence regarding the safety and efficacy of combined SHD+LAAO procedure, while also providing insights in gaps in knowledge and future directions for the evolvement of this field.

Optimal management of high bleeding risk patients undergoing percutaneous coronary interventions: Where do we stand?

Percutaneous coronary interventions (PCI) are the mainstay of treating obstructive coronary artery disease. However, procedural planning and individualization of the procedure is necessary for different patient phenotypes to optimize outcomes. Specifically, post-PCI pharmacotherapy with antiplatelets complicates the management of patients at high bleeding risk due to comorbidities, such as atrial fibrillation. Aiming to limit post-procedural adverse events and reduce the procedure-related bleeding risk, several novel technologies and hypotheses have been tested in clinical practice. Such frontiers include limiting the duration of dual antiplatelet therapy or even prescribing single regimens, using drug-coated balloons for performing the intervention and the effect of imaging-guided PCI in optimizing stent expansion. Furthermore, specific instruction in different patient phenotypes, such as atrial fibrillation and chronic kidney disease, are emerging, as despite both pathologies being considered at high bleeding risk, one size does not fit all. Thus, our review will provide all the recent updates on the field as well as algorithms and expert opinions on how to manage this, particularly common, phenotype of patient.

Atrial Functional Mitral Regurgitation: From Diagnosis to Current Interventional Therapies.

Mitral regurgitation (MR) is one of the most common valvular pathologies worldwide, contributing to the morbidity and mortality of several cardiovascular pathologies, including heart failure (HF). Novel transcatheter treatment for MR has given the opportunity for a safe and feasible alternative, to surgery, in order to repair the valve and improve patient outcomes. However, after the results of early transcatheter edge-to-edge repair (TEER) trials, it has become evident that subcategorizing the mitral regurgitation etiology and the left ventricular function, in patients due to undergo TEER, is of the essence, in order to predict responsiveness to treatment and select the most appropriate patient phenotype. Thus, a novel MR phenotype, atrial functional MR (AFMR), has been recently recognized as a distinct pathophysiological entity, where the etiology of the regurgitation is secondary to annular dilatation, in a diseased left atrium, with preserved left ventricular function. Recent studies have evaluated and compared the outcomes of TEER in AFMR with ventricular functional MR (VFMR), with the results favoring the AFMR. In specific, TEER in this patient substrate has better echocardiographic and long-term outcomes. Thus, our review will provide a comprehensive pathogenesis and mechanistic overview of AFMR, insights into the echocardiographic approach of such patients and pre-procedural planning, discuss the most recent clinical trials and their implications for future treatment directions, as well as highlight future frontiers of research in the setting of TEER and transcatheter mitral valve replacement (TMVR) in AFMR patients.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients Following Acute Coronary Syndromes: From Lipid Lowering and Plaque Stabilization to Improved Outcomes.

Lipid lowering, with the use of statins after an acute coronary syndrome (ACS), is a cornerstone, well-established strategy for the secondary prevention of ischemic events in this high-risk cohort. In addition to the positive effect on lipid levels, statins have also been linked to improved atherosclerotic plaque characteristics, such as plaque regression and inflammation reduction, associated with the extent of reduction in LDL-C. The recent emergence of PCSK9 inhibitors for the management of dyslipidemia and the more extensive lipid lowering provided by these agents may provide better prevention for ACS patients when initiated after the ACS event. Several trials have evaluated the immediate post-ACS initiation of PCSK9 inhibitors, which has shown, to date, beneficial results. Furthermore, PCSK9 inhibitors have been linked with positive plaque remodeling and associated mortality benefits, which makes their use in the initial management strategy of such patients appealing. Therefore, in this review, we will analyze the rationale behind immediate lipid lowering after an ACS, report the evidence of PCSK9 inhibition immediately after the ACS event and the available data on plaque stabilization, and discuss treatment algorithms and clinical perspectives for the use of these agents in this clinical setting.

Transcatheter Structural Heart Interventions in the Acute Setting: An Emerging Indication.

Structural heart disease is increasingly prevalent in the general population, especially in patients of increased age. Recent advances in transcatheter structural heart interventions have gained a significant following and are now considered a mainstay option for managing stable valvular disease. However, the concept of transcatheter interventions has also been tested in acute settings by several investigators, especially in cases where valvular disease comes as a result of acute ischemia or in the context of acute decompensated heart failure. Tested interventions include both the mitral and aortic valve, mostly evaluating mitral transcatheter edge-to-edge repair and transcatheter aortic valve implantation, respectively. This review is going to focus on the use of acute structural heart interventions in the emergent setting, and it will delineate the available data and provide a meaningful discussion on the optimal patient phenotype and future directions of the field.

Computed Tomography Angiography Identified High-Risk Coronary Plaques: From Diagnosis to Prognosis and Future Management.

CT angiography has become, in recent years, a main evaluating modality for patients with coronary artery disease (CAD). Recent advancements in the field have allowed us to identity not only the presence of obstructive disease but also the characteristics of identified lesions. High-risk coronary atherosclerotic plaques are identified in CT angiographies via a number of specific characteristics and may provide prognostic and therapeutic implications, aiming to prevent future ischemic events via optimizing medical treatment or providing coronary interventions. In light of new evidence evaluating the safety and efficacy of intervening in high-risk plaques, even in non-flow-limiting disease, we aim to provide a comprehensive review of the diagnostic algorithms and implications of plaque vulnerability in CT angiography, identify any differences with invasive imaging, analyze prognostic factors and potential future therapeutic options in such patients, as well as discuss new frontiers, including intervening in non-flow-limiting stenoses and the role of CT angiography in patient stratification.

Prognostic role of discordance between quantitative flow ratio and visual estimation in revascularization guidance.

Aims: Revascularization guided by functional severity has presented improved outcomes compared with visual angiographic guidance. Quantitative flow ratio (QFR) is a reliable angiography-based method for functional assessment. We sought to investigate the prognostic value of discordance between QFR and visual estimation in coronary revascularization guidance. Methods and results: We performed offline QFR analysis on all-comers undergoing coronary angiography. Vessels with calculated QFR were divided into four groups based on the decision to perform or defer percutaneous coronary intervention (PCI) and on the QFR result, i.e.: Group A (PCI-, QFR > 0.8); Group B (PCI+, QFR ≤ 0.8); Group C (PCI+, QFR > 0.8); Group D (PCI-, QFR ≤ 0.8). Patients with at least one vessel falling within the disagreement groups formed the discordance group, whereas the remaining patients formed the concordance group. The primary endpoint was the composite endpoint of cardiovascular death, myocardial infarction, and ischaemia-driven revascularization. Overall, 546 patients were included in the study. Discordance between QFR and visual estimation was found in 26.2% of patients. After a median follow-up period of 2.5 years, the discordance group had a significantly higher rate of the composite outcome (hazard ratio: 3.34, 95% confidence interval 1.99-5.60, P < 0.001). Both disagreement vessel Groups C and D were associated with increased cardiovascular risk compared with agreement Groups A and B. Conclusion: Discordance between QFR and visual estimation in revascularization guidance was associated with a worse long-term prognosis. Our results highlight the importance of proper patient selection for intervention and the need to avoid improper stent implantations when not dictated by a comprehensive functional assessment.

Interventional management of mitral regurgitation and sleep disordered breathing: "Catching two birds with one stone".

Sleep disordered breathing (SDB), mostly constituting of obstructive and central sleep apnea (OSA and CSA, respectively), is highly prevalent in the general population, and even more among patients with cardiovascular disease, heart failure (HF) and valvular heart disease, such as mitral regurgitation (MR). The coexistence of HF, MR and SDB is associated with worse cardiovascular outcomes and increased morbidity and mortality. Pulmonary congestion, as a result of MR, can exaggerate and worsen the clinical status and symptoms of SDB, while OSA and CSA, through various mechanisms that impair left ventricular dynamics, can promote left ventricular remodelling, mitral annulus dilatation and consequently MR. Regarding treatment, positive airway pressure devices used to ameliorate symptoms in SDB also seem to result in a reduction of MR severity, MR jet fraction and an improvement of left ventricular ejection fraction. However, surgical and transcatheter interventions for MR, and especially transcatheter edge to edge mitral valve repair (TEER), seem to also have a positive effect on SDB, by reducing OSA and CSA-related severity indexes and improving symptom control. The purpose of this review is to provide a comprehensive analysis of the common pathophysiology between SDB and MR, as well as to discuss the available evidence regarding the effect of SDB treatment on MR and the effect of mitral valve surgery or transcatheter repair on both OSA and CSA.

Inferior epigastric artery as a landmark for transfemoral TAVI. Optimizing vascular access?

OBJECTIVES: This study sought to investigate whether the site of common femoral artery (CFA) cannulation in regard to the inferior epigastric artery (IEA) is associated with the incidence of vascular complications in patients undergoing transfemoral aortic valve implantation (TAVI). BACKGROUND: Vascular access complications are a main issue during TAVI and have been associated with significant increase of morbidity and mortality. The need for establishment of reliable predictors for these serious events remains important. METHODS: A total of 90 patients, who had undergone TAVI, were retrospectively studied. Vascular complications were defined as major and minor according to the Valve Academic Research Consortium (VARC) criteria. Patients were divided into high cannulation site (CS) group and low CS group depending on the common femoral artery puncture site position, in regards to the most inferior border of the IEA. RESULTS: Vascular complications were significantly more frequent in the high CS group versus the low CS group (32.3% vs. 11.9%, P = 0.039). High cannulation remained an independent predictor of vascular complications after adjustment for known risk factors (OR: 4.827, CI: 1.441-16.168; P = 0.011). CONCLUSIONS: In patients undergoing transfemoral TAVI, arterial puncture above the most inferior border of the IEA is associated with vascular complications.

Impact of cardiometabolic risk factors on major cardiovascular events in patients with familial combined hyperlipidemia.

BACKGROUND: Familial combined hyperlipidemia (FCH) is an inherited lipid disorder associated with premature cardiovascular disease. It has not been established whether the cardiometabolic risk factors, which frequently accompany FCH, such as diabetes, metabolic syndrome (MetS) and hypertension, modulate cardiovascular risk in FCH patients. METHODS AND RESULTS: In this single-center, retrospective study, 695 FCH patients with adequate follow-up were enrolled (mean age, 48.9 years; 455 male). Risk factors including lipid levels were evaluated before the initiation of treatment. Acute myocardial infarction (AMI) and cardiovascular death were recorded during a mean follow-up of 9 years. The combined endpoint (AMI and/or cardiovascular death) occurred in 41 patients (5.9% of the total). Those FCH patients who reached the combined endpoint had lower high-density lipoprotein cholesterol (HDL-C) than those who did not, but levels of other lipid variables were similar. Presence of hypertension, diabetes or MetS was a predictor of the combined endpoint on univariate Kaplan-Meier analysis (all P<0.005). Multivariate Cox proportional analysis showed that hypertension and MetS were associated with the combined endpoint independently of age, gender, HDL-C and presence of coronary artery disease at enrollment (adjusted hazard ratios [HRs], 3.00; 95% confidence interval [CI]: 1.46-6.17, P=0.003; HR, 2.43; 95CI%: 1.11-5.33, P=0.026, respectively). CONCLUSIONS: Cardiometabolic risk factors such as hypertension and MetS are independent predictors of major cardiovascular events in FCH patients.

Coronary sinus narrowing therapy: A "Reducer" for angina and beyond.

Refractory Angina (RA) is an increasingly common clinical diagnosis, in which patients unsuitable for further percutaneous or surgical procedures experience anginal symptoms, despite receiving optimal medical therapy. This clinical condition challenges the everyday activities and diminishes the quality of life of these patients. A wide variety of novel therapies for this type of angina are being investigated for clinical use. One of them is coronary sinus narrowing, which is performed as a percutaneous interventional procedure using catheter-delivered device, the Reducer. The device is implanted in the coronary sinus creating a physical narrowing and a pressure gradient in the sinus. This intervention improves the impaired blood flow in the ischemic regions of the heart leading to the relief of the anginal symptoms and, therefore, the overall clinical improvement of these patients. Several clinical trials have established both the safety and efficacy of the coronary sinus Reducer, while ongoing trials are aiming to further establish the procedure's safety and efficiency in both RA and other cardiovascular diseases, such as coronary microvascular dysfunction. This review aims to discuss the pathophysiology and the role of the coronary sinus Reducer in RA, the clinical trials documenting its safety and efficacy, as well as the future perspectives of this procedure among cardiovascular diseases.

Prognostic Value of Post-PCI Angiography-Derived Fractional Flow Reserve: A Systematic Review and Meta-Analysis of Cohort Studies.

The post-percutaneous coronary intervention (post-PCI) fractional flow reserve (FFR) can detect suboptimal PCI or residual ischemia and potentially lead to fewer adverse clinical outcomes. We sought to investigate the predictive value of the angiography-derived FFR for adverse cardiovascular events in patients after PCI. We conducted a comprehensive search of electronic databases, MEDLINE, EMBASE, and the Cochrane Library, for studies published until March 2023 that investigated the prognostic role of angiography-derived fractional flow reserve values after PCI. We investigated the best predictive ability of the post-PCI angiography-derived FFR and relative risk (RR) estimates with 95% confidence intervals (CIs) between post-PCI angiography-derived FFR values and adverse events. Thirteen cohort studies involving 6961 patients (9719 vascular lesions; mean follow-up: 2.2 years) were included in this meta-analysis. The pooled HR of the studies using specific cut-off points for post-PCI angiography-derived FFR was 4.13 (95% CI, 2.92-5.82) for total cardiovascular events, while the pooled HRs for target vessel revascularization, cardiac death, target vessel myocardial infarction, and target lesion revascularization were 6.87 (95% CI, 4.93-9.56), 6.17 (95% CI, 3.52-10.80), 3.98 (95% CI, 2.37-6.66) and 6.27 (95% CI, 3.08-12.79), respectively. In a sensitivity analysis of three studies with 1789 patients assessing the predictive role of the post-PCI angiography-derived FFR as a continuous variable, we found a 58% risk reduction for future adverse events per 0.1 increase in the post-PCI angiography-derived FFR value. In conclusion, post-PCI angiography-derived FFR is an effective tool for predicting adverse cardiovascular events and could be potentially used in decision making, both during PCI and in the long-term follow-up.

Intravascular Imaging in Ultra-Low or Zero-Contrast Percutaneous Coronary Interventions: The Time Is Now?

Ultra-low contrast percutaneous coronary interventions (ULPCIs) are a novel field of interventional cardiology, aiming to reduce the risk of contrast-induced nephropathy (CIN), which is a well-described adverse event after angiography. CIN is a well-described adverse event following PCI, especially in high-risk patients, i.e., patients with an already deteriorating renal function or chronic kidney disease, as well as patients of advanced age or requiring an increased amount of contrast during their intervention. Among the techniques described for ULPCI procedures, intravascular imaging guidance seems a promising option, as it allows lesion recognition and characterization, stent implantation, and PCI optimization. Intravascular ultrasound (IVUS) is the modality most commonly used, as it does not require contrast injection, contrary to optical coherence tomography (OCT). Several clinical trials, assessing IVUS in the context of ULPCI, have shown that it can be safely used in this setting while offering a substantial reduction in contrast media volume, as well as renal adverse outcomes. This review aims to describe the need for ULPCI and technical considerations regarding the use of intravascular imaging in this setting, as well as analyze the available evidence from clinical trials regarding the safety and efficacy of IVUS-ULPCI, in order to provide a comprehensive summary for practicing physicians.