Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin-angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition. A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.

Novel 3D versus traditional transesophageal echocardiography techniques: Defining differences in the diagnosis of infective endocarditis.

BACKGROUND: Despite the availability of current antibiotic and surgical treatment options, infective endocarditis (IE) remains associated with a high mortality rate. Even though two-dimensional (2D) transesophageal echocardiography (TOE) is a major criteria in the diagnosis of IE, it is constrained by the single-plane orientation. Since three-dimensional (3D) TOE provides a comprehensive understanding of the cardiac architecture by allowing for a realistic visualization of the underlying structures in 3D space, it has attracted considerable interest in recent years. AIM: The purpose of this narrative review is to discuss the advantages and pitfalls of 3D TOE in patients with IE, as well as to address emerging photo-realistic 3D techniques that have the potential to enhance the visualization of cardiac structures in this setting. RESULTS: According to recent research, 3D TOE acquisitions outperform 2D acquisitions in terms of vegetation identification accuracy and embolism risk assessment. By reporting a variety of findings that are missed with 2D TOE, but which are validated by surgical examination, 3D TOE further improves the ability to identify endocarditis complications on both native and prosthetic valves. In addition to conventional 3D TOE, future developments in 3D technology led to the development of transillumination and tissue-transparency rendering, which may improve anatomical understanding and depth perception. Due to the use of both conventional and novel 3D techniques, there are more patients who require surgical intervention, indicating that 3D TOE may have a clinical relevance on the surgical management. CONCLUSION: 3D TOE might fill the gaps left by 2D TOE in the diagnosis of IE.

A Late-Detected Paraganglioma in a Young Patient with Resistant Hypertension and Severe Aortic Regurgitation-A Case Report and Review of the Literature.

BACKGROUND: Paraganglioma is a rare neuroendocrine tumor derived from chromaffin cells. The overproduction of catecholamines accounts for the presenting symptoms and cardiovascular complications. The clinical presentation frequently overlaps with the associated cardiac diseases, delaying the diagnosis. Multimodality imaging and a multidisciplinary team are essential for the correct diagnosis and adequate clinical management. CASE SUMMARY: A 37-year-old woman with a personal medical history of long-standing arterial hypertension and radiofrequency ablation for atrioventricular nodal reentry tachycardia presented with progressive exertional dyspnea and elevated blood pressure values, despite a comprehensive pharmacological treatment with six antihypertensive drugs. The echocardiography showed a bicuspid aortic valve and severe aortic regurgitation. The computed tomography angiography revealed a retroperitoneal space-occupying solid lesion, with imaging characteristics suggestive of a paraganglioma. The multidisciplinary team concluded that tumor resection should be completed first, followed by an aortic valve replacement if necessary. The postoperative histopathology examination confirmed the diagnosis of paraganglioma. After the successful resection of the tumor, the patient was asymptomatic, and the intervention for aortic valve replacement was delayed. DISCUSSION: This was a rare case of a late-detected paraganglioma in a young patient with resistant hypertension overlapping the clinical presentation and management of severe aortic regurgitation. A multimodality imaging approach including transthoracic and transesophageal echocardiography, computed tomography, and magnetic resonance imaging had an emerging role in establishing the diagnosis and in guiding patient management and follow-up. The resection of paraganglioma was essential for the optimal timing of surgical correction for severe aortic regurgitation. We further reviewed various cardiovascular complications induced by pheochromocytomas and paragangliomas.

The Degree of Stent Apposition Measured by Stent Enhancement at the Level of the Side Branch as a Novel Predictor of Procedural Success in Left Main PCI.

BACKGROUND: Stent enhancement techniques allow adequate visualization of stent deformation or incomplete stent expansion at the ostium of the side branch. Measuring the stent enhancement side branch length (SESBL) could reflect procedural success in terms of optimal stent expansion and apposition with better long-term outcomes. A longer SESBL may reflect a better stent apposition at the polygon of confluence and at the side branch (SB) ostium. METHODS: We evaluated 162 patients receiving the left main (LM) provisional one-stent technique and measured the SESBL, dividing them into two groups: SESBL≤ 2.0 mm and SESBL > 2.0 mm. RESULTS: The mean SESBL was 2.0 ± 1.2 mm. More than half of the bifurcations had both main and side branch lesions (Medina 1-1-1) (84 patients, 51.9%) and the length of the SB disease was 5.2 ±1.8 mm. Kissing balloon inflation (KBI) was performed in 49 patients (30.2%). During follow-up (12 months), there was a significantly higher rate of cardiac death in the SESBL ≤ 2.0 mm group (p = 0.02) but no significant difference in all major adverse cardiovascular events (MACEs) (p = 0.7). KBI did not influence the outcomes (p = 0.3). CONCLUSION: Suboptimal SESBL is positively correlated with worse outcomes and SB compromise. This novel sign could aid the LM operator to assess the level of stent expansion at the ostium of the SB in the absence of intracoronary imaging.

The Role of Multimodality Imaging in the Diagnosis and Follow-Up of Malignant Primary Cardiac Tumors: Myxofibrosarcoma-A Case Report and Literature Review.

Cardiac tumors are a very rare but heterogenous group of diseases that may reveal themselves through a variety of nonspecific cardiac symptoms that may pose a challenge to the diagnostic process. Myxofibrosarcoma is a particularly rare type of cardiac tumor that carries a poor prognosis, thus making accurate and timely diagnosis essential. A 61-year-old woman presented with fatigue and shortness of breath during mild exercise, symptoms that have progressively worsened during the previous year. Multimodality imaging consisting of transthoracic and transesophageal echocardiography (TTE and TEE), cardiac magnetic resonance (CMR), cardiac computer tomography (CCT), and fluorodeoxyglucose positron emission computer tomography (18F-FDG PET-CT) was used for the diagnosis and postoperative follow-up of a myxofibrosarcoma.

Clinical Characteristics and Outcomes following Percutaneous Coronary Intervention in Unprotected Left Main Disease: A Single-Center Study.

Background: Hemodynamically significant unprotected left main (LM) coronary artery disease is a high-risk clinical condition because of the large area of myocardium at risk, and it requires prompt revascularization. Percutaneous coronary intervention (PCI) is an appropriate alternative to coronary artery bypass grafting (CABG) for revascularization of unprotected LM disease in patients with low-to-intermediate anatomic complexity or when the patient refuses CABG after adequate counseling by the heart team. Methods: We retrospectively evaluated 201 patients receiving left main (LM) provisional one-stent or two-stent procedures, and we assessed the clinical characteristics and outcomes of patients undergoing unprotected LM PCI. Results: The mean age was 66.5 ± 9.9 years, and 72% were male. The majority of the subjects presented several cardiovascular risk factors, among which arterial hypertension (179 patients, 89.5%) and dyslipidemia (173 patients, 86.5%) were the most frequent. Out of all patients, 162 (81.8%) underwent revascularization by using the one-stent technique, while the two-stent technique was used in 36 patients (18.2%). The median value of fractional flow reserve (FFR) of the side branch was 0.9 [0.85-0.95], and 135 patients (67.1%) showed a value of FFR > 0.8. One hundred nine patients (54.2%) had a stent enhancement side branch length (SESBL) > 2, with median values of 2.5 mm2 [2.1-3]. Regarding angiographic parameters, the LM area as assessed by intravascular ultrasound (IVUS) or optical coherence tomography (OCT) and the grade of stenosis as assessed by quantitative coronary angiography (QCA) were similar between groups. However, patients who required revascularization by using the two-stent technique presented more frequently with intermediate rather than low SYNTAX scores (69.4% vs. 28.4%, p < 0.0001). Also, the same group required kissing balloon inflation (KBI) more frequently (69.4% vs. 30%, p < 0.001). There were no differences regarding the success of revascularization between the use of the one-stent or two-stent technique. FFR was able to predict a SESBL > 2 mm. The cut-off value for FFR to afford the highest degree of sensitivity (74.5%) and specificity (47%) for a SESBL > 2 was >0.86, indicating a moderate accuracy (AUC = 0.61, 95% CI 0.525-0.690, p = 0.036). Conclusions: Unprotected left main PCI is a safe and effective revascularization option amongst a complex and morbid population. There were no differences regarding the success of revascularization between the use of the one-stent or two-stent technique, and there was no significant impact of KBI on side branch FFR measurements but lower side branch FFR values were correlated with angiographic side branch compromise.

Predictive Value of Collagen Biomarkers in Advanced Chronic Kidney Disease Patients.

Patients with chronic kidney disease have an increased risk of all-cause death. The value of collagen biomarkers such as procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III N-terminal peptide (P3NP), in end-stage renal disease (ESRD), has not yet been defined (in the literature and in clinics). The purpose of this study was to determine the potential value of these new biomarkers in the prediction of mortality in this population. Plasma PICP and P3NP levels were determined in 140 patients with ESRD, not yet on dialysis, who were followed up for 36 ± 5.3 months. During follow-up, 58 deaths were recorded (41.4%), with the majority of them being cardiovascular deaths (43, 74.13%). Using the ROC curve, the cut-off value for the prediction of mortality for PICP was 297.31 µg/L, while for P3NP, the cut-off value was 126.67 µg/L. In univariate analysis, a value of PICP above the cut-off point was associated with a fivefold increased risk of mortality (hazard ratio (HR) 5.071, 95% confidence interval 1.935-13.29, p = 0.001) and a value of P3NP above the cut-off point was associated with a twofold increased risk of mortality (HR 2.089, 95% CI 1.044-4.178, p = 0.002). In a multivariable Cox proportional hazards model, PICP values remained independent predictors of mortality (HR 1.22, 95% CI 1.1-1.31, p < 0.0001). Our data suggest that the collagen biomarker PICP is an independent predictor of mortality in ESRD patients who are not yet on dialysis.

The Role of Echocardiography in the Diagnosis of Cardiac Involvement in a Rare Systemic Condition: The Carcinoid Heart Disease: A Case Report and Review of Literature.

Carcinoid heart disease is a rare presentation of the carcinoid syndrome, which is caused by excessive tumoral hormone production and the abundant release of vasoactive substances with systemic expressions. A 62-year-old woman presented with flushing, diarrhea, weight loss, and right-sided heart failure symptoms. Specific carcinoid heart disease features were identified using transthoracic and transesophageal echocardiography at the tricuspid and pulmonic valves. Biomarkers, 99mTc-Tektrotyd scintigraphy, SPECT-CT, and a biopsy later confirmed the diagnosis, and the patient began treatment for the underlying condition.

Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting for Non-Protected Left Main Coronary Artery Disease: 1-Year Outcomes in a High Volume Single Center Study.

INTRODUCTION: There is clear evidence of a significant reduction in all major cardiovascular adverse events (MACE) by coronary artery bypass grafting (CABG) in left main coronary artery stenosis (LMCS), but revascularization by percutaneous coronary artery intervention (PCI) shows an increasingly important role as an alternative to CABG. Several recent trials aiming to test the difference in mortality between the two types of revascularization found conflicting data. The aim of this study is to determine whether PCI is non-inferior to CABG with respect to the occurrence of MACE at 1 year in patients with significant LMCS. MATERIAL AND METHODS: We prospectively enrolled 296 patients with chronic or acute coronary syndromes and significant LM stenosis. The angiography that recommended the revascularization procedure was used for the calculation of the Syntax II score, in order to classify the patients as low-, intermediate- or high-risk. Low- and high-risk patients were revascularized with either PCI or CABG, according to current guidelines, and were included in the subgroup S1. The second subgroup (S0) included intermediate-risk patients (Syntax II score 23-32), in whom the type of revascularization was chosen depending on the decision of the heart team or the patient preference. Patients were monitored according to the chosen mode of revascularization-PCI or CABG. LM revascularization was performed in all the patients. Clinical endpoints included cardiac death, myocardial infarction, need for revascularization and stroke. Patients were evaluated at 1 year after revascularization. Event rates were estimated using the Kaplan-Meier analysis in time to the first event. RESULTS: At 1-year follow-up, a primary endpoint occurred in 35/95 patients in the CABG group and 37/201 in the PCI group. There were no significant differences between the 2 treatment strategies in the 1-year components of the end-point. However, a tendency to higher occurrence of cardiac death (HR = 1.48 CI (0.55-3.9), p = 0.43), necessity of repeat revascularization (HR = 1.7, CI (0.81-3.6), p = 0.16) and stroke (HR = 1.52, CI (1.15-2.93), p = 0.58) were present after CABG. Contrariwise, although without statistical significance, MI was more frequent after PCI (HR = 2, CI (0.78-5.2), p = 0.14). The Kaplan-Meier estimates in subgroups demonstrated the same tendency to higher rates for cardiac death, repeat revascularization and stroke after CABG, and higher rates of MI after PCI. Although without statistical significance, patients with an intermediate-risk showed a slightly lower risk of MACE after PCI than CABG. With the exception of dyslipidemia and gender, other cardiovascular risk factors were in favor of CABG (CKD, obesity). CONCLUSION: In patients with LMCS, PCI with drug-eluting stents was non-inferior to CABG with respect to the composite of cardiac death, myocardial infarction, repeat revascularization and stroke at 1 year, even in patients with intermediate Syntax II risk score.

Impact of Three-Dimensional Strain on Major Adverse Cardiovascular Events after Acute Myocardial Infarction Managed by Primary Percutaneous Coronary Intervention-A Pilot Study.

BACKGROUND: Three-dimensional speckle-tracking echocardiography (3D-STE) allows simultaneous assessment of multidirectional components of strain. However, there are few data on its usefulness to predict prognosis in patients with acute myocardial infarction (AMI). The objective of our pilot study was to evaluate the prognostic value of four different 3D-STE parameters (global longitudinal strain (GLS-3D), global circumferential strain (GCS-3D), global radial strain (GRS-3D), and global area strain (GAS)) in AMI, after successful revascularization by primary PCI. METHODS: We enrolled 94 AMI patients (66 ± 13 years, 56% men) who underwent coronary angiography. All patients had been 3D-STE assessed and followed-up for 1 year for the occurrence of MACE. RESULTS: A total of 25 MACE were recorded over follow-up. Cut-off values of -17% for GAS (HR = 3.1, 95% CI: 1.39-6.92, p = 0.005), -12% for GCS-3D (HR = 3.06, 95% CI: 1.36-6.8, p = 0.006), -10% for GLS-3D (HR = 3.04, 95% CI: 1.36-6.78, p = 0.006), and 25% for GRS-3D (HR = 2.89, 95% CI: 1.29-6.46, p = 0.009) showed moderate accuracy in MACE prediction. Multivariate regression showed that GAS (HR = 1.1, 95% CI: 1.03-1.16), GLS-3D (HR = 1.13, 95% CI: 1.03-1.26), and GCS-3D (HR = 1.13, 95% CI: 1.03-1.23) remained independent predictors of MACE (HR = 1.07, 95% CI: 1.01-1.14 for GAS, and HR = 1.1, 95% CI: 1.01-1.2 for GCS-3D). However, post hoc power analysis indicated adequate sample size (power of 80%) only for GAS and GCS-3D for the ROC curve analysis and for GAS, GCS-3D, and GRS-3D for the log-rank test. CONCLUSION: Patients with AMI might benefit from early risk stratification with the aid of 3D-STE measurements, particularly GAS and GCS-3D, but larger studies are necessary to determine the optimal cut-off values to predict MACE.

Frenemies within: An Endocarditis Case in Behçet's Disease.

A 57-year female patient diagnosed with Behçet's disease, on azathioprine, was noticed to have at a routine examination antinuclear and antiphospholipid antibodies. An overlapping lupus-like syndrome was diagnosed; hydroxychloroquine and aspirin were added. Three years later, the patient presented with dyspnea and sweating, with no fever. A cardiac bruit was noted; a giant vegetation was detected by echocardiography. Laboratory revealed severe thrombocytopenia, antiphospholipid antibodies and low complement. Blood cultures were positive for Abiotrophia defectiva serology and also revealed a chronic Coxiella burnetii infection. Antibiotic therapy, low-dose anticoagulation and control of the underlying disease mildly improved the platelet count, which fully recovered only after cardiac valve replacement. However, the Behçet's disease, initially quiescent, flared after the therapy of infections. We discuss potential links between Behçet's disease and the occurrence of antinuclear and antiphospholipid antibodies and Coxiella endocarditis in this setting. We also highlight the differences between the endocarditis in Behçet's disease, antiphospholipid syndrome, Coxiella burnetii and Abiotrophia defectiva infection, respectively. Intracellular infections may modify the presentation of autoimmune diseases. Confounding clinical features of Coxiella persistent infection and non-bacterial thrombotic endocarditis in Behçet's disease warrant further insight.