Transcatheter Tricuspid Valve Interventions: A Triumph for Transcatheter Procedures?

Tricuspid regurgitation (TR) is a common valvular pathology, estimated to affect 1.6 million people in the United States alone. Even though guidelines recommend either medical therapy or surgical treatment for TR, the misconception of TR as a benign disease along with the high mortality rates of surgical intervention led to undertreating this disease and commonly describing it as a "forgotten" valve. Recently, the development of transcatheter interventions for TR show promising potential for use in the clinical setting. There are currently few approved and numerous tested percutaneously delivered devices, which can be categorized, based on their mechanism of action, to either valve repair or valve replacement procedures. Both procedures were tested in clinical trials and show an echocardiographic reduction in TR sustained for at least 1 year after the procedure, as well as symptom relief and functional improvement of the patients. Device selection should be personalized, taking into consideration the anatomy of each valve and the available options at each heart center. Moreover, appropriate patient selection and timing of the procedure are also crucial for the success of the procedure. In this review, we analyze the clinical trials available for all devices currently approved or tested, aiming to provide a comprehensive summary of the most recent evidence in the field of transcatheter TR interventions.

A network meta-analysis of the antithrombotic strategies in patients with atrial fibrillation and percutaneous coronary interventions: Focus on bleeding.

BACKGROUND: We performed a network meta-analysis of randomized controlled trials comparing non-vitamin K antagonist oral anticoagulant (NOAC)-based versus vitamin K antagonists (VKA)-based regimens in patients with atrial fibrillation (AF) and acute coronary syndromes or PCI, aiming to examine the precise impact of recently established antithrombotic strategies on major bleeding as primary end-point and other safety and efficacy as secondary end-points. METHODS: A literature search was conducted for randomized controlled trials. Our search took place in three major databases. The primary endpoint of our study was bleeding. To combine direct and indirect evidence across trials, a frequentist network meta-analysis with a random-effects model was used. RESULTS: Five studies were found eligible for the meta-analysis enrolling a total of 11,542 patients. Five studies (N = 4903 patients) contributed to the network. Compared to the triple antithrombotic therapy (TAT)-based VKA, only the dual antithrombotic therapy (DAT) based NOAC reduced the bleeding (RR 0.57, 95%CI 0.40-0.82). There was no statistically significant difference between DAT-based VKA (RR = 0.66, 95%CI = 0.40-1.09) or TAT-based NOAC (RR = 0.80, 95%CI = 0.43-1.49). DAT-based NOAC ranked best (P-score = 0.91), followed by DAT-based VKA (P-score = 0.67), TAT-based NOAC (P-score = 0.40), and TAT-based VKA (P-score = 0.03). CONCLUSION: The network meta-analysis of four antithrombotic strategies, demonstrated that in patients with AF undergoing PCI the combination of DAT-based NOAC is associated with a significantly lower risk of major bleeding events. This strategy does not seem to be less effective in terms of prevention of ischemic events compared to the other regimens.

Broad Electrocardiogram Syndromes Spectrum: From Common Emergencies to Particular Electrical Heart Disorders.

Electrocardiogram (ECG) still remains a very useful diagnostic method in modern cardiology. Its broad availability, noninvasiveness and good sensitivity explain why it plays a capital role in the very beginning of the process of diagnosis for every patient, with or without cardiac-related complaints. For the practitioner, good training in ECG interpretation is mandatory. Sometimes, the ECG trace reveals particular aspects that may cause confusion and complicate decision-making. In this article, we present several less common situations underlying the general context and ECG features. The syndromes studied have a high pathological significance and may range from acute emergencies that call for a rapid therapeutical response to chronic syndromes that require prolonged observation, monitoring and risk stratification.

The prognostic value of speckle tracking echocardiography in patients with end stage renal disease on dialysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with a higher incidence of cardiovascular death especially as the disease progresses and patients are on long-term dialysis treatment. Left ventricular (LV) dysfunction and cardiac deformation measured by speckle tracking echocardiography seem to play an important prognostic role in several different specific populations. OBJECTIVE: Τhe prognostic value of strain analysis measurements, including the novel diastolic parameters such as left atrial (LA) strain, in patients with end-stage renal disease on dialysis (stage 5 CKD). METHODS: 67 patients (mean age 62.3 ± 11.8, 65.7% men) with stage 5 CKD (45 on hemodialysis and 22 on peritoneal dialysis) were enrolled in the study protocol. The mean duration of dialysis was 102.48 ± 84.98 months. Mean follow-up lasted seven years. RESULTS: Most of the study population had normal or mildly impaired systolic function with a mean LV ejection fraction of 49.17% (± 10.41) while 70% of patients had impaired LV global longitudinal strain, mean 14.35% (± 4.49). Regarding LA strain parameters the mean LA reservoir, LA conduit, and LA contractile reserve were 24.11% (± 12.61), 10.56% (± 5.88), and 13.60% (± 9.15) respectively. Thus 50% of the population had impaired LA strain. Logistic regression analysis showed that of the various echocardiographic parameters LV ejection fraction, LV global longitudinal strain, and the conduit phase of LA strain were significantly associated with total prognosis (p = 0.009, p = 0.007, p = 0.05). The conduit element of LA strain was the strongest predictor among them, when adjusted for age (OR = 0.77 p = 0.04). CONCLUSIONS: Left ventricular diastolic dysfunction is an important prognostic factor in patients with advanced CKD on long-term dialysis, without known CAD. The novel echocardiographic parameters such as LA strain could add valuable information to the overall cardiac evaluation of this specific population.

Intravascular Lithotripsy as Bail-Out in an Acute Coronary Syndrome Patient With Severe Underexpansion of a Previously Implanted Stent.

A 67-year-old male presented with non-ST-segment elevation myocardial infarction. Angiography showed severe restenosis within the previously (before 2 years) implanted 2 stents (3 x 24 mm) in the right coronary artery. Severe calcification was evident angiographically and after multiple dilations with noncompliant balloons, the focal underexpansion of the stent remained. A 3-mm x 12-mm intravascular lithotripsy balloon was used and after the third series of 10 pulses, full expansion of the stent was observed. Postdilation of the stenosis with noncompliant and drug-eluting balloons was accompanied by excellent angiographical result with no residual stenosis. The patient was discharged free of symptoms and remains uneventful with no complications. The case demonstrates the feasibility of intravascular lithotripsy in acute coronary syndromes related to stent underexpansion due to severe calcification that is refractory to other conventional techniques.

Buprenorphine withdrawal induced takotsubo cardiomyopathy: A series of unfortunate events.

This case report describes a 64-year-old female with history of previous intravenous drug abuse on opioid substitution treatment with buprenorphine, who presented to the emergency department with angina and electrocardiographic findings suggestive of acute coronary syndrome. Echocardiography and left ventriculography were indicative of takotsubo cardiomyopathy, probably attributed to abrupt discontinuation of buprenorphine. Opioid withdrawal leads to sympathetic hyperactivity and increased catecholamine release, which in our case triggered takotsubo cardiomyopathy presentation. .

Stroke and presence of patent foramen ovale in sickle cell disease.

Sickle cell disease (SCD) is an inherited monogenic hemoglobinopathy characterized by formation of sickle erythrocytes under conditions of deoxygenation. Sickle erythrocytes can lead to thrombus formation and vaso-occlusive episodes that may result in hemolytic anemia, pain crisis and multiple organ damage. Moreover, SCD is characterized by endothelial damage, increased inflammatory response, platelet activation and aggravation, and activation of both the intrinsic and the extrinsic coagulation pathways. Cerebrovascular events constitute an important clinical complication of SCD. Children with SCD have a 300-fold higher risk of acute stroke and by the age of 45 about 25% of patients have suffered an overt stoke. Management and prevention of stroke in patients with SCD is not well defined. Moreover, the presence of patent foramen ovale (PFO) increases the risk of the occurrence of an embolic cerebrovascular event. The role of PFO closure and antiplatelet or anticoagulation therapy has not been well investigated. Moreover, during COVID-19 pandemic and taking into account the increased rates of thrombotic events and the difficulties in blood transfusion, management of SCD patients is even more challenging and difficult, since data are scarce regarding stroke occurrence and management in this specific population in the COVID-19 era. This review focuses on pathophysiology of stroke in patients with SCD and possible treatment strategies in the presence of PFO.

The Effect of Dobutamine Stress Testing on Vortex Formation Time in Patients Evaluated for Ischemia.

Vortex formation time (VFT) is a dimensionless index used to quantify duration of vortex ring formation during diastole. We sought to investigate the effect of pharmaceutical stress on VFT in patients evaluated for ischemia. For this purpose, a standard dobutamine stress echo (DSE) protocol was performed in 50 consecutive patients, and VFT was calculated at rest and at peak. VFT was calculated from echocardiography measurements using a previously developed mathematical equation. VFTi was calculated as the percentage of change of VFTpeak, compared with VFTrest. Mean VFTrest was 2.46 (0.73) and mean VFTpeak 1.67 (0.57) with mean VFTi - 30.0% (19.8). In 14 (28%) patients, an ischemic response (DSE+) was documented. VFTi was significantly lower in DSE+ patients a finding which remained significant in the multivariate analysis after adjusting for age, sex, hypertension, diabetes, history of coronary artery disease, and relative increase of heart rate during stress. Graphical Abstract.

Long-term clinical outcomes of coronary artery bypass graft surgery compared to those of percutaneous coronary intervention with second generation drug eluting stents in patients with stable angina and an isolated lesion in the proximal left anterior descending artery.

OBJECTIVES: We compared the long-term outcomes of percutaneous coronary intervention with second-generation drug-eluting stents (PCI-DES) and coronary artery bypass graft surgery (CABG) with the left internal mammary artery in stable angina patients with isolated single-vessel proximal left anterior descending artery (pLAD) disease. BACKGROUND: Long-term outcomes of second-generation PCI-DES and CABG in isolated pLAD lesions have not been extensively studied. METHODS: We included 631 PCI-DES patients and 379 CABG patients. Unadjusted and adjusted hazard ratios (HRs) were derived for major adverse cardiac events (MACEs), their components (cardiac death, nonfatal myocardial infarction [MI] not attributed to a non-target vessel, target-lesion revascularization), and patient-related outcome (PRO, composed of all-cause mortality, any MI, any revascularization). RESULTS: In the unadjusted and adjusted analyses, no significant difference was observed between the two groups at follow-up (mean:4.6 ± 2.5 years) for MACEs (HR: 1.45, 95% CI: 0.92-2.28, p = .11; HR:1.43, 95% CI: 0.91-2.26, p = .13), PRO (HR: 1.18, 95%CI: 0.86-1.61, p = .30; HR: 1.18, 95% CI: 0.86-1.62, p = .31), cardiac death (HR: 0.97, 95% CI: 0.46-2.05, p = .93; HR: 0.79, 95% CI: 0.36-1.72, p = .56) and MI (HR: 1.43, 95% CI: 0.49-4.13, p = .51; HR: 1.57, 95% CI: 0.53-4.64, p = .42). Compared with CABG, PCI-DES had a borderline significantly greater risk of repeat revascularization (HR: 1.99, 95% CI: 1.00-3.94, p = .05; HR: 1.95, 95% CI: 0.98-3.9, p = .06). Angina recurred more often after PCI (p < .001), whereas more arrhythmias developed after CABG (p = .02). PCI-DES resulted in fewer in-hospital complications (p < .001) and shorter hospitalizations (p < .001). CONCLUSIONS: The long-term clinical outcomes of second-generation PCI-DES and CABG in patients with stable angina and isolated pLAD disease were comparable.

Cardiac Masses: The Role of Cardiovascular Imaging in the Differential Diagnosis.

Cardiac masses are space occupying lesions within the cardiac cavities or adjacent to the pericardium. They include frequently diagnosed clinical entities such as clots and vegetations, common benign tumors such as myxomas and papillary fibroelastomas and uncommon benign or malignant primary or metastatic tumors. Given their diversity, there are no guidelines or consensus statements regarding the best diagnostic or therapeutic approach. In the past, diagnosis used to be made by the histological specimens after surgery or during the post-mortem examination. Nevertheless, evolution and increased availability of cardiovascular imaging modalities has enabled better characterization of the masses and the surrounding tissue. Transthoracic echocardiography using contrast agents can evaluate the location, the morphology and the perfusion of the mass as well as its hemodynamic effect. Transesophageal echocardiography has increased spatial and temporal resolution; hence it is superior in depicting small highly mobile masses. Cardiac magnetic resonance and cardiac computed tomography are complementary providing tissue characterization. The scope of this review is to present the role of cardiovascular imaging in the differential diagnosis of cardiac masses and to propose a step-wise diagnostic algorithm, taking into account the epidemiology and clinical presentation of the cardiac masses, as well as the availability and the incremental value of each imaging modality.

The role of 'halo sign' for the accurate quantification of atrial septal defect size with 3D TEE.

In patients undergoing percutaneous closure of secundum atrial septal defect, the device selection is decided based on three-dimensional transesophageal echocardiography (3D TEE) measurements and two-dimensional balloon stretched diameter measurements; more importantly balloon sizing. The purpose of the study was to assess whether in patients with "halo-sign", defined as increased tissue thickness at the edge of the ASD rims, there is an agreement between 3D TEE and 2D balloon stretched diameter aiming to avoidance of balloon sizing. Forty consecutive patients who underwent closure of a single, without complex anatomy ASD were included. 3D and 2D TEE datasets were acquired and analyzed offline. Planimetry was used to calculate circumference derived diameter of ASD from 3D datasets. Patients were classified according to the presence of the "halo sign" and the agreement between circumference derived diameter and balloon stretched diameter was examined. Forty consecutive patients who underwent closure of a single, without complex anatomy ASD were included. 3D and 2D TEE datasets were acquired and analyzed offline. Planimetry was used to calculate circumference derived diameter of ASD from 3D datasets. Patients were classified according to the presence of the "halo sign" and the agreement between circumference derived diameter and balloon stretched diameter was examined. Higher correlation and lower median absolute difference between 3D TEE measurements and 2D stretched balloon diameter was found in patients with "halo sign". In patients with the "halo sign" mean diameter difference was non-significant. On the contrary statistically significant difference was found in patients without the "halo sign". Significant difference was also found when comparing mean difference in the two patient groups. ASD sizing by 3D echocardiography, is accurate in patients with halo sign and it correlates well with the balloon sizing method. This study justifies further investigation concerning the reliability of 3D imaging for the selection of the ASD device size with a view to avoid balloon sizing, decrease procedural time and thus simplify the procedure.

Impact of increased venous pressure on kidney function and mortality in cardiovascular patients with preserved ejection fraction.

Background: Right but not left ventricular hemodynamic parameters have been found to be independently associated with adverse renal outcomes in patients with acute decompensated heart failure (HF).Aim: To investigate the hemodynamic profile of patients without acute decompensated heart failure and left ventricular ejection fraction >50% referred for elective left and right heart catheterization and to correlate left and right filling pressures, stroke volume and arterial blood pressure to renal function parameters. Subsequently, we tested the hypothesis that right ventricle and left ventricle hemodynamic parameters can predict all-cause mortality in our non-HF subjects.Methods: Between October 2009 and November 2010, 151 consecutive patients referred for elective left and right heart catheterization were studied and consequently followed up for a mean period of 8 years in order to identify all-cause mortality. Patient's initial cohort was subdivided in two groups according to right atrial pressure. The RAPRLOW group (Right Atrium Pressure ≤ 9 mmHg) and the RAPRHIGH group (Right Atrium Pressure > 9mmHg)Results: No correlation between blood pressure, pulmonary capillary wedges pressure, cardiac index, stroke volume and stroke volume index (SVI), and parameters of kidney function was observed. However, a weak, although, significant correlation between right atrial pressure (RAP) and modification of diet in renal disease (MDRD) (r = -0.202; p = .014) could be detected. RAPRLOW patients had a statistically significant lower MDRD value of 16.6 mL/min/1.73 m2 than RAPRHIGH patients. Increased RAP (HR = 2.03; 95% [CI]: 1.05 to 3.9; p = .025) and age (HR = 1.08, 95% [CI] 1.04-1.12, p < .001) independently predicted all-cause mortality during follow up.Conclusions: Our study demonstrates that right ventricular preload affects renal function in patients with preserved systolic function and that neither aortic systolic pressure nor left ventricle pressure indices were related to estimated glomerular filtration rate. Furthermore, we demonstrate for the first time that an increased RAP is able to predict a worse prognosis in patients with preserved ejection fraction independently of well-established risk factors, such as blood pressure and SVI.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches.

BACKGROUND: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. OBJECTIVE: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. METHOD: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. RESULTS: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). CONCLUSION: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation.

BACKGROUND: Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed. OBJECTIVES/METHODS: The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation. RESULTS: Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk. CONCLUSIONS: Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.

Biomarkers Associated with Atrial Fibrosis and Remodeling.

Atrial fibrillation is the most common rhythm disturbance encountered in clinical practice. Although often considered as solely arrhythmic in nature, current evidence has established that atrial myopathy constitutes both the substrate and the outcome of atrial fibrillation, thus initiating a vicious, self-perpetuating cycle. This myopathy is triggered by stress-induced (including pressure/volume overload, inflammation, oxidative stress) responses of atrial tissue, which in the long term become maladaptive, and combine elements of both structural, especially fibrosis, and electrical remodeling, with contemporary approaches yielding potentially useful biomarkers of these processes. Biomarker value becomes greater given the fact that they can both predict atrial fibrillation occurrence and treatment outcome. This mini-review will focus on the biomarkers of atrial remodeling (both electrical and structural) and fibrosis that have been validated in human studies, including biochemical, histological and imaging approaches.

Biomarkers in Aortic Valve Stenosis and their Clinical Significance in Transcatheter Aortic Valve Implantation.

Aortic valve stenosis is one of the most common valvular heart disorders and the prevalence will rise as the population ages. Once symptomatic patients with aortic valve stenosis tend to fare worse with high mortality rates. Aortic valve replacement is indicated in these patients and besides the standard surgical replacement, a less invasive approach, transcatheter aortic valve implantation, has gained momentum and has showed promising and solid results in patients with high surgical risk. An important aspect of evaluating patients with aortic valve stenosis is the ability to choose the best possible candidate for the procedure. In addition, predicting the short and long-term clinical outcomes after the valve replacement could offer the treating physicians a better insight and provide information for optimal therapy. Biomarkers are biological parameters that can be objectively measured and evaluated as indicators of normal biological processes and are easily monitored. The aim of this review is to critically assess some of the most widely used biomarkers at present (natriuretic peptides, troponins, C-reactive protein) and provide an insight in novel biomarkers that are currently being investigated (galectin-3, growth differentiation factor-15, microRNAs) for possible diagnostic and prognostic use in aortic valve stenosis and transcatheter aortic valve implantation respectively.

Overview of coronary artery variants, aberrations and anomalies.

Coronary artery anomalies and variants are relatively uncommon congenital disorders of the coronary artery anatomy and constitute the second most common cause of sudden cardiac death in young competitive athletes. The rapid advancement of imaging techniques, including computed tomography, magnetic resonance imaging, intravascular ultrasound and optical coherence tomography, have provided us with a wealth of new information on the subject. Anomalous origin of a coronary artery from the contralateral sinus is the anomaly most frequently associated with sudden cardiac death, in particular if the anomalous coronary artery has a course between the aorta and the pulmonary artery. However, other coronary anomalies, like anomalous origin of the left coronary artery from the pulmonary artery, atresia of the left main stem and coronary fistulae, have also been implicated in cases of sudden cardiac death. Patients are usually asymptomatic, and in most of the cases, coronary anomalies are discovered incidentally during coronary angiography or on autopsy following sudden cardiac death. However, in some cases, symptoms like angina, syncope, heart failure and myocardial infarction may occur. The aims of this article are to present a brief overview of the diverse coronary variants and anomalies, focusing especially on anatomical features, clinical manifestations, risk of sudden cardiac death and pathophysiologic mechanism of symptoms, as well as to provide valuable information regarding diagnostic workup, follow-up, therapeutic choices and timing of surgical treatment.