Transthyretin cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: experience of a single center.

BACKGROUND: Even if prevalent among patients with severe aortic stenosis (AS), the clinical suspicion for transthyretin cardiac amyloidosis (ATTR-CA) remains difficult in this subset. We report our single center experience on ATTR-CA detection among TAVR candidates to provide insights on the prevalence and clinical features of dual pathology as compared to lone AS. METHODS: Consecutive severe AS patients undergoing transcatheter aortic valve replacement (TAVR) evaluation at a single center were prospectively included. Those with suspected ATTR-CA based on clinical assessment underwent 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy. The RAISE score, a novel screening tool with high sensitivity for ATTR-CA in AS, was retrospectively calculated to rule-out ATTR-CA in the remaining patients. Patients were categorized as follow: "ATTR-CA+": patients with confirmed ATTR-CA at DPD bone scintigraphy; "ATTR-CA-": patients with negative DPD bone scintigraphy or a negative RAISE score; "ATTR-CA indeterminate": patients not undergoing ATTR-CA assessment with a positive RAISE score. The characteristics of ATTR-CA+ and ATTR-CA- patients were compared. RESULTS: Of 107 included patients, ATTR-CA suspicion was posed in 13 patients and confirmed in six. Patients were categorized as follow: 6 (5.6%) ATTR-CA+, 79 (73.8%) ATTR-CA-, 22 (20.6%) ATTR-CA indeterminate. Excluding ATTR-CA indeterminate patients, the prevalence of ATTR-CA was 7.1% (95% CI 2.6-14.7%). As compared to ATTR-CA - patients, ATTR-CA + patients were older, had higher procedural risk and more extensive myocardial and renal damage. They had higher left ventricle mass index and lower ECG voltages, translating into a lower voltage to mass ratio. Moreover, we describe for the first time bifascicular block as an ECG feature highly specific of patients with dual pathology (50.0% vs. 2.7%, P<0.001). Of note, pericardial effusion was rarely found in patients with lone AS (16.7% vs. 1.2%, P=0.027). No difference in procedural outcomes was observed between groups. CONCLUSIONS: Among severe AS patients, ATTR-CA is prevalent and presents with phenotypic features that may aid to differentiate it from lone AS. A clinical approach based on routine search of amyloidosis features might lead to selective DPD bone scintigraphy with a satisfactory positive predictive value.

Cardiac imaging for the prediction of sudden cardiac arrest in patients with heart failure.

The identification of heart failure (HF) patients at risk for arrhythmic sudden cardiac arrest (SCA) is a major challenge in the cardiovascular field. In addition to optimal medical treatment for HF, implantable cardioverter defibrillator (ICD) is currently recommended to prevent SCA in patients with reduced left ventricular ejection fraction (LVEF). The indication for an ICD implantation, in addition to HF etiology, New York Health Association (NYHA) class and life expectancy, mainly depends on LVEF value at echocardiography. However, the actual role of LVEF in the prediction of SCA has recently been debated, while newer multimodality imaging techniques with increased prognostic accuracy have been developed. Speckle tracking imaging allows the quantification of mechanical dispersion, a marker of electrophysiological heterogeneity predisposing to malignant arrhythmias, while advanced cardiac magnetic resonance techniques such as myocardial T1-mapping and extracellular volume fraction assessment allow the evaluation of interstitial diffuse fibrosis. Nuclear imaging is helpful for the appraisal of sympathetic nervous system dysfunction, while newer computed tomography techniques assessing myocardial delayed enhancement allow the identification of focal myocardial scar. This review will focus on the most modern advances in the field of cardiovascular imaging along with its applications for the prediction of SCA in patients with HF. Modern artificial intelligence applications in cardiovascular imaging will also be discussed.

An integrated approach to cardioprotection in lymphomas.

In potentially curable cancers, long-term survival depends not only on the successful treatment of the malignancy but also on the risks associated with treatment-related toxicity, especially cardiotoxicity. Malignant lymphomas affect patients at any age, with acute and late toxicity risks that could have a severe effect on morbidity, mortality, and quality of life. Although our understanding of chemotherapy-associated and radiotherapy-associated cardiovascular disease has advanced considerably, new drugs with potential cardiotoxicity have been introduced for the treatment of lymphomas. In this Review, we summarise the mechanisms of treatment-related cardiac injury, available clinical data, and protocols for optimising cardioprotection in lymphomas. We discuss ongoing research strategies to advance our knowledge of the molecular basis of drug-induced and radiation-induced toxicity. Additionally, we emphasise the potential for personalised follow-up and early detection, including the role of biomarkers and novel diagnostic tests, highlighting the role of the cardio-oncology team.

Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey.

AIM: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. METHODS AND RESULTS: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%-35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. CONCLUSION: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.

Impact of computed-tomography defined sarcopenia on outcomes of older adults undergoing transcatheter aortic valve implantation.

BACKGROUND: The adoption of Computed tomography (CT)-defined sarcopenia to risk stratify transcatheter aortic valve implantation (TAVI) candidates remains limited by a lack of both standardized definition and evidence of independent value over currently adopted mortality prediction tools. METHODS: 391 consecutive TAVI patients with pre-procedural CT scan were included (81 â€‹± â€‹6 years, 57.5% male, STS-PROM score 4.4 â€‹± â€‹3.6%) and abdominal muscle retrospectively quantified. The two definitions of radiologic sarcopenia previously adopted in TAVI studies were compared (psoas muscle area [PMA] at the L4 vertebra level: "PMA-sarcopenia"; indexed skeletal muscle area at the L3 vertebra level: "SMI-sarcopenia"). The primary endpoint was longer available-term all-cause mortality. Secondary endpoints were Valve Academic Research Consortium-2-defined in-hospital and 30-day outcomes. RESULTS: SMI- and PMA-sarcopenia were present in 192 (49.1%) and 117 (29.9%) patients, respectively. After a median of 24 (12-30) months follow-up, 83 (21.2%) patients died. PMA-(adj-HR 1.81, 95%CI 1.12-2.93, p â€‹= â€‹0.015), but not SMI-sarcopenia (adj-HR 1.23, 95%CI 0.76-2.00, p â€‹= â€‹0.391), was associated with all-cause mortality independently of age, sex and in-study outcome predictors (atrial fibrillation, hemoglobin, history of peripheral artery disease, cancer and subcutaneous adipose tissue). PMA-defined sarcopenia provided additive prognostic value over current post-TAVI mortality risk estimators including STS-PROM (p â€‹= â€‹0.001), Euroscore II (p â€‹= â€‹0.025), Charlson index (p â€‹= â€‹0.025) and TAVI2-score (p â€‹= â€‹0.020). Device success, early safety, clinical efficacy and 30-day all-cause death were unaffected by sarcopenia status regardless of definition. CONCLUSIONS: PMA-sarcopenia (but not SMI-sarcopenia) is predictive of 2 year mortality among TAVI patients. The prognostic information provided by PMA-sarcopenia is independent of the tools currently adopted to predict post-TAVI mortality in clinical practice.

Cardiovascular magnetic resonance of cardiac tumors and masses.

Cardiac masses diagnosis and treatment are a true challenge, although they are infrequently encountered in clinical practice. They encompass a broad set of lesions that include neoplastic (primary and secondary), non-neoplastic masses and pseudomasses. The clinical presentation of cardiac tumors is highly variable and depends on several factors such as size, location, relation with other structures and mobility. The presumptive diagnosis is made based on a preliminary non-invasive diagnostic work-up due to technical difficulties and risks associated with biopsy, which is still the diagnostic gold standard. The findings should always be interpreted in the clinical context to avoid misdiagnosis, particularly in specific conditions (e.g., infective endocarditis or thrombi). The modern multi-modality imaging techniques has a key role not only for the initial assessment and differential diagnosis but also for management and surveillance of the cardiac masses. Cardiovascular magnetic resonance (CMR) allows an optimal non-invasive localization of the lesion, providing multiplanar information on its relation to surrounding structures. Moreover, with the additional feature of tissue characterization, CMR can be highly effective to distinguish pseudomasses from masses, as well as benign from malignant lesions, with further differential diagnosis of the latter. Although histopathological assessment is important to make a definitive diagnosis, CMR plays a key role in the diagnosis of suspected cardiac masses with a great impact on patient management. This literature review aims to provide a comprehensive overview of cardiac masses, from clinical and imaging protocol to pathological findings.

Post cardiac injury syndromes: diagnosis and management.

Post cardiac injury syndromes (PCIS) are becoming increasingly common, due to the growing number of cardiovascular procedures (cardiac surgery, percutaneous interventions) and the high burden of cardiovascular diseases such as acute coronary syndromes. This review aims to provide an overview of the main clinical characteristics of PCIS, along with their management in clinical practice.

Cardiometabolic Risk, Part 1: Chemotherapy and Radiotherapy - Old Foes Still Threatening Cancer Survivors?

Long-term cancer survivors are at high risk of developing cardiac complications from the treatments, both systemic agents and thoracic irradiation, received to cure the primary tumor. Modern advances, particularly in the field of radiotherapy, aim to reduce the risk of cardiovascular disease. Also, new diagnostic tools increasingly improve their efficacy in early detection of the preclinical treatment-induced cardiac damage. In this review, we summarize the mechanisms of radiotherapy- and chemotherapy-induced cardiac injury, the available clinical data, the strategies to mitigate cardiac exposure with modern radiotherapy and the current diagnostic tools for an early detection and prompt management of these complications in long-term cancer survivors.

Safety of lung stereotactic ablative radiotherapy for the functioning of cardiac implantable electronic devices.

BACKGROUND AND PURPOSE: The prevalence of patients with a cardiac implantable device (CIED) developing cancer and requiring a course of radiotherapy (RT) is increasing remarkably. Previously published reports agree that standard and conventionally fractionated RT is usually safe for CIEDs, but no "in-vivo" reports are available on the potential effects of thoracic stereotactic ablative radiotherapy (SABR) regimens to CIEDs functioning. The purpose of our study is therefore to evaluate the effects of SABR on CIEDs (pacemakers [PM] or implantable cardiac defibrillators [ICD]) in a cohort of patients affected by primary or metastatic lung lesions. MATERIALS AND METHODS: We retrospectively collected all CIED-bearing patients undergoing SABR between 2007 and 2019 at our Institution. All CIEDs were interrogated before and after the SABR course to check for any malfunction. Prescription dose, beam energy and maximum dose (Dmax) to CIEDs were retrieved for each patient. Electrical records of the CIEDs were reviewed by the medical records. RESULTS: Thirty-four consecutive patients (24 with a PM and 10 with an ICD), who underwent 38 separate SABR courses, were included in the study. Eight patients (24%) were PM-dependent. Prescription dose of SABR ranged 26-60 Gy in 1-8 fractions, with a photon energy ranging 6-to-10 MV (76.3% and 23.7%, respectively) and a median Dmax to CIEDs of 0.17 Gy (range 0.04-1.97 Gy). Electrical parameters were stable in post-treatment device programming visits and no transient or persistent alteration of the CIED function was recorded in any patient. No inappropriate interventions were recorded in the 10 ICD-bearing patients during the treatment fractions. CONCLUSIONS: Thoracic SABR proved to be safe for CIEDs when the dose is kept <2 Gy and the beam energy is ≤10 MV, irrespective of the pacing-dependency and of the CIED type.

Subclinical Left Ventricular Dysfunction in Severe Obesity and Reverse Cardiac Remodeling after Bariatric Surgery.

AIM: Obesity is associated with an increased cardiovascular risk. This study aimed to assess the role of echocardiography in the early detection of subclinical cardiac abnormalities in a cohort of obese patients with a preserved ejection fraction (EF) undergoing bariatric surgery. METHODS AND RESULTS: Forty consecutive severely obese patients (body mass index≥35 kg/m2) referring to our center for bariatric surgery were enrolled in this prospective cohort study. Despite a baseline EF of 61% ± 3%, almost half patients (43%) had a systolic dysfunction (SD) defined as global longitudinal strain (GLS)>-18%, and most of them (60%) had left ventricular hypertrophy (LVH) or concentric remodeling (CR). At 10-months after surgery, body weight decreased from 120 ± 15 kg to 83 ± 12 kg, body mass index from 44 ± 5 kg/m2 to 31 ± 5 kg/m2 (both P < 0.001). Septal and left ventricular posterior wall thickness decreased respectively from 10 ± 1 mm to 9 ± 1 mm (P = 0.004) and from 10 ± 1 mm to 9 ± 1 mm (P = 0.007). All systolic parameters improved: EF from 61% ± 3% to 64% ± 3% (P = 0.002) and GLS from -17% ± 2% to -20% ± 1% (P < 0.001). Epicardial fat thickness reduction (from 4.7 ± 1 mm to 3.5 ± 0.7 mm, P < 0.001) correlated with the reduction of left atrial area (P < 0.001 R = 0.35) and volume (P = 0.02 R = 0.25). Following bariatric surgery, we observed a reduced prevalence of LVH/CR (before 60%, after 22%, P = 0.001) and a complete resolution of preclinical SD (before 43%, after 0%, P < 0.001). Moreover, a postoperative reduction of at least 30 kg correlated with regression of septal hypertrophy (P < 0.001). CONCLUSIONS: Obese patients candidate to bariatric surgery have an high prevalence of preclinical SD and LVH/CR, early detectable with echocardiography. Bariatric surgery is associated with reverse cardiac remodeling; it might also have a preventive effect on atrial fibrillation occurrence by reducing its substrate.

Update on diagnosis and management of neoplastic pericardial disease.

INTRODUCTION: Pericardial neoplasms are uncommon, mostly due to secondary involvement of the pericardium by extracardiac tumors. Clinical presentation is nonspecific, frequently leading to a delayed diagnosis. Moreover, both benign and malignant pericardial tumors may be associated with myocardial infiltration and mechanical compression of cardiac chambers, possibly precipitating clinical conditions. Pericardial tumors are indeed a diagnostic and therapeutic clinical challenge. AREAS COVERED: This review aims to provide an overview of the main clinical characteristics of pericardial tumors, along with their management in clinical practice. EXPERT COMMENTARY: Multimodality imaging (echocardiography, chest X-ray, CT, CMR, and PET) enable full characterization of pericardial neoplasms. An individualized strategy should be developed by a multidisciplinary team including cardiologists, oncologists, radiologists, and cardiac surgeons.

In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis.

BACKGROUND: One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients. CLINICAL CASE: We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively. CONCLUSION: In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

S-ICD lead dislodgement in a young isometric athlete: A rare complication.

The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to transvenous ICD in patients who do not need cardiac pacing. We report the case of a young isometric athlete who received S-ICD for primary prevention of sudden death. Lead dislodgement and myopotential noise oversensing during isometric training led to inappropriate shock, and a surgical revision was performed. During the procedure, strong fibrous adhesions were found, requiring polytetrafluoroethylene dilator sheaths. The S-ICD was finally reimplanted. Despite continued isometric training, no more myopotential oversensing occurred after 1-year follow-up. The present case highlights the possible higher risks of lead complication in an isometric athlete and the uncommon effort in removing an old-generation subcutaneous defibrillator lead.

A single cystatin C determination before coronary angiography can predict short and long-term adverse events.

BACKGROUND: Cystatin C (CyC) role in the detection of contrast induced acute kidney injury (CIAKI) is controversial. This study assessed whether a single CyC determination before coronary angiography (CA)could predict CIAKI and long-term adverse events. METHODS: CyC was assessed before CA in 713 consecutive patients. CIAKI was the primary endpoint, defined as ≥0.3 mg/dl creatinine (sCR) increase at 48 h or ≥50% in 7-days. All-cause death, cardiovascular (CV)death and MACE (acute coronary syndrome, acute pulmonary edema,CV death) were secondary endpoints. Re-hospitalization, in-hospital death and worsening renal function were tertiary endpoints. RESULTS: CIAKI occurred in 47 (6.7%) patients. ROC analysis showed a good accuracy of CyC in the prediction of CIAKI (AUC 0.82,p < 0.01), compared with baseline sCR and sCR-eGFR (AUC 0.70 and 0.75 respectively, both p < 0.01). CyC was associated with 10-year CV-death, all-cause death and MACEs (AUC 0.76,0.74 and 0.64 respectively,all p < 0.01). A CyC cut-off value of 1.4 mg/L was not only accurate in predicting or ruling-out CIAKI following CA (97% negative predictive value, 84% specificity), but also useful as a prognostic marker for 10-year adverse events (50% vs.16% all cause mortality, 29% vs.3% CV death, 39% vs.13% MACE,all p < 0.01), re-hospitalizations (54% vs.35%,p < 0.01) and worsening renal function (34% vs.19%,p < 0.01). The strongest and independent risk factor for 10-year CV death was baseline CyC>1.4 mg/L (HR 17.3, 95% CI 1.94-155.1). CONCLUSIONS: A baseline determination of CyC before CA can accurately rule out CIAKI and predict adverse events in the long term. CIAKI can be ruled out before CA in 97% patients with a CyC value < 1.4 mg/L.

Same-day CIED implantation and discharge: Is it possible? The E-MOTION trial (Early MObilization after pacemaker implantaTION).

BACKGROUND: Despite the increasing number of cardiac implantable electronic devices (CIED) procedures worldwide, no guideline assessed postoperative mobilization protocols. Lacking evidences in literature, many centers require 24-hour immobilization and bed rest to minimize the risk of pacing lead (PL) dislodgement. Prolonged immobilization may futilely delay discharge, induce pain and reduced joint mobility especially in elderly patients. We examined whether early mobilization at 3-h after CIED surgery would result in higher complication rates, compared with standard 24-hour immobilization. METHODS: Consecutive patients undergoing CIED implantation were randomized to early (3-h) mobilization protocol with an arm sling support (E-motion group, EMG) vs. standard (24-h) immobilization (control group, CG). The primary end-point was 24-month PL dislodgement. Secondary safety end-point was any major intra-procedural complication (cardiac perforation, pericardial tamponade, valve damage, haemothorax, pneumothorax, myocardial infarction, peripheral embolus, TIA/stroke or death). RESULTS: Among 200 enrolled patients, 86% underwent pacemaker implantation (28% single-chamber, 72% dual-chamber device), 14% underwent ICD implantation (75% single-chamber, 25% dual-chamber device). PL fixation was mostly passive (97% atrial PL, 88% ventricular PL), without differences between EMG and CG (p = 0.99). No differences were observed in the incidence of 24-month PL dislodgement (3% in the EMG vs. 4% in the CG, p = 0.99). No major intra-procedural complications were observed. CONCLUSIONS: Early mobilization at 3-h following CIED surgery is safe and feasible compared with standard immobilization and is not associated with an increased risk of intra-procedural complications or 24-month lead dislodgment. So, same-day implantation and discharge might be possible.

Transcatheter Aortic Valve Implantation in Patients With Advanced Chronic Kidney Disease.

Advanced chronic kidney disease (CKD) is associated with poor outcomes in patients who underwent surgical aortic valve replacement, whereas its prognostic role in transcatheter aortic valve implantation (TAVI) remains unclear. This study aimed to investigate outcomes in patients with advanced CKD who underwent TAVI. A total of 1,904 consecutive patients who underwent balloon-expandable TAVI in 33 centers between 2007 and 2012 were enrolled in the Italian Transcatheter Balloon-Expandable Valve Implantation Registry. Advanced CKD was defined according to the estimated glomerular filtration rate: 15 to 29 ml/min/1.73 m2 stage 4 (S4), <15 ml/min/1.73 m2 stage 5 (S5). Edwards Sapien or Sapien-XT prosthesis were used. The primary end point was all-cause mortality during follow-up. Secondary end points were major adverse cardiac events at 30 days and at follow-up, defined with Valve Academic Research Consortium 2 criteria. A total of 421 patients were staged S5 (n = 74) or S4 (n = 347). S5 patients were younger and had more frequently porcelain aorta and a lower incidence of previous stroke. Periprocedural and 30-day outcomes were similar in S5 and S4 patients. During 670 (±466) days of follow-up, S5 patients had higher mortality rates (69% vs 39%, p <0.01) and cardiac death (19% vs 9%, p = 0.02) compared with S4 patients. Male gender (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.2 to 2.2), left ventricular ejection fraction <30% (HR 2.3, 95% CI 1.3 to 4), atrial fibrillation (HR 1.4, 95% CI 1.0 to 1.9), and S5 CKD (HR 1.5, 95% CI 1.0 to 2.1) were independent predictors of death. In conclusion, TAVI in predialytic or dialytic patients (i.e., S5) is independently associated with poor outcomes with more than double risk of death compared with patients with S4 renal function. Conversely, in severe CKD (i.e., S4) a rigorous risk stratification is required to avoid the risk of futility risk.