Safety of ultra-low contrast coronary angiography in patients with acute kidney injury.

BACKGROUND: Ultra-low contrast administration during coronary angiography has been previously shown to be feasible and safe among patients with stable chronic kidney disease. In the present study, we investigate the safety of ultra-low contrast coronary angiography in patients with pre-existing acute kidney injury (AKI). METHODS: The study was a retrospective single-center evaluation of hospitalized patients who had AKI and required coronary angiography. Ultra-low contrast use was defined as ≤18 mL of contrast media. RESULTS: The cohort consisted of a case series of eight inpatients with AKI who required coronary angiography. The mean age was 57 (±16) years and half were females. All patients had chronic kidney disease with a mean baseline estimated glomerular filtration rate of 34 (±17) mL/min/1.73 m2. The mean creatinine before angiography was 3 (±1) mg/dL and volume of contrast administered was 14 (±4) mL. One patient had a 0.1 mg/dL increase in creatinine during admission, and no patients had further AKI up to 1-week postprocedure. CONCLUSIONS: The current data suggest that ultra-low contrast coronary angiography can be safely performed in patients with pre-existing AKI The study should be viewed as hypothesis-generating due to its small sample size. A larger cohort is required to validate the results.

Sodium-glucose co-transporter-2 inhibitors in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the prognosis of cancer. Diabetes mellitus (DM) has been shown to have a negative effect on patients treated with ICIs. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective antidiabetic therapies associated with reduced all-cause mortality and cardiovascular (CV) outcomes. OBJECTIVE: To evaluate the prognostic value of SGLT2i on all-cause mortality and cardiotoxicity among patients treated with ICIs. METHODS: We performed a retrospective analysis of patients diagnosed with cancer and type 2 DM (DM2) and treated with ICIs at our center. Patients were divided into two groups according to baseline treatment with or without SGLT2i. The primary endpoint was all-cause mortality and the secondary endpoint was MACE, including myocarditis, acute coronary syndrome, heart failure, and arrhythmia. RESULTS: The cohort included 119 patients, with 24 (20%) patients assigned to the SGLT2i group. Both groups exhibited a comparable prevalence of cardiac risk factors, although the SGLT2i group displayed a higher incidence of ischemic heart disease. Over a median follow-up of 28 months, 61 (51%) patients died, with a significantly lower all-cause mortality rate in the SGLT2i group (21% vs. 59%, p = 0.002). While there were no significant differences in MACE, we observed zero cases of myocarditis and atrial fibrillation in the SGLT2i, compared to 2 and 6 cases in the non-SGLT2i group. CONCLUSIONS: SGLT2i therapy was associated with a lower all-cause mortality rate in patients diagnosed with cancer and DM2 and treated with ICIs. Further studies are needed to understand the mechanism and evaluate its benefit on cardiotoxicity.

The prognostic value of beta-1 blockers in patients with non-small-cell lung carcinoma treated with pembrolizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC). Beta-adrenergic activation contributes to cancer initiation and progression. While non-selective beta-blocker were found to improve the efficacy of ICIs therapy, the role of beta-1 (ß1)-selective -blocker (ß1B) in lung cancer patients is unknown. OBJECTIVE: To evaluate the effect of ß1B on overall survival (OS) and progression-free survival (PFS) in patients diagnosed with mNSCLC and treated with pembrolizumab. METHODS: We performed a retrospective analysis of patients diagnosed with mNSCLC and treated with first-line pembrolizumab at our center. RESULTS: Of 200 eligible patients, 53 (27%) were pretreated with ß1B. Patients in the ß1B cohort were older (73 ± 8 vs. 67 ± 10 years, p < 0.001) with a higher prevalence of cardiac risk factors and cardiovascular (CV) diseases including ischemic heart disease (32% vs. 16%, p = 0.010), heart failure (9% vs. 3%, p = 0.043) and atrial fibrillation (23% vs. 3%, p < 0.001). Compared to the non-ß1B group, patient pretreated with ß1B had a significant shorter median OS (12 vs. 24 months, p = 0.004) and PFS (6 vs. 8 months, p < 0.001). In a multivariate analysis, including all CV risk factors and diseases, the use of baseline ß1B was a strong and independent predictor for accelerated disease progression (HR 1.92, 95%CI 1.32-2.79, p < 0.001) and shorter OS (HR 1.8, 95%, CI 1.18-2.75, p = 0.007). CONCLUSIONS: The use of baseline ß1B showed a strong and independent association for shorter OS and PFS in patients diagnosed with mNSCLC and treated with pembrolizumab.

Percutaneous debulking of tricuspid valve infective endocarditis vegetations using a large bore manual aspiration device - AlphaVac.

Most infectious endocarditis patients can be managed medically. However, non-responders to antibiotics and ongoing sequelae such as septic emboli, may require mechanical interventions. AngioVac (Angiodynamics, Latham, NY, USA) is a percutaneous aspiration device used for removal of thrombi, emboli, masses, and vegetations. Main drawbacks are the requirement for a perfusionist, two large-bore accesses, and meticulous de-airing. These drawbacks make the procedure more time-consuming and possibly increase the risk of complications. AlphaVac (Angiodynamics) omits the motor element, thereby overcoming several of the limitations. In the current report, we describe two cases of percutaneous aspiration of tricuspid valve vegetations using AlphaVac. Learning objective: To consider manual percutaneous aspiration of infective valvular vegetations using the AlphaVac cannula in case of insufficient response to antibiotics or for prevention of emboli.

Baseline Left Ventricle Longitudinal Strain as a Predictor for Clinical Improvement Following Coronary Sinus Reducer Implantation.

Coronary sinus narrowing device (reducer) implantation has emerged as an effective treatment to improve the quality of life and functional capacity in patients suffering from disabling refractory angina. Left ventricle global longitudinal strain (LV-GLS) is a useful tool for early diagnosis of subclinical cardiac injury and an independent predictor for coronary artery disease. We aimed to investigate whether LV-GLS could help predict clinical improvement after coronary sinus reducer implantation. LV-GLS assessments were performed at baseline and 6 months after reducer implantation in consecutive patients treated for refractory angina. Patients were divided into 2 groups based on reduced (<17% absolute value) or preserved baseline LV-GLS. Clinical improvement was defined as an increase of ≥25 m in the 6-minute walk test (6MWT) at follow-up. Overall, 41 patients were included, 31 in the reduced LV-GLS group and 10 in the preserved LV-GLS group. The mean age was 68 ± 8 years, with only 2 female patients (5%). Baseline characteristics did not differ significantly between the 2 groups. Univariable analysis revealed that LV-GLS was the only significant predictor for 6MWT improvement. Baseline preserved LV-GLS reduced the likelihood of 6MWT improvement by 82% (odds ratio 0.18 [0.04 to 0.83], p = 0.029). A significant increase in 6MWT (307 ± 97 m to 343 ± 92 m, p = 0.017) was observed in the reduced LV-GLS group, compared with a decrease in the preserved LV-GLS group (378 ± 86 m to 361 ± 123 m, p = 0.651). In conclusion, reduced LV-GLS may serve as a marker for potential clinical improvement in patients with refractory angina treated with reducer. Larger clinical trials are needed to establish its role.

Implications of Indeterminate and Determined Etiologies Leading to Small Left Atria.

BACKGROUND: Small left atria (LA) is associated with an increased risk of mortality. OBJECTIVES: To determine whether the attributed risk of mortality is influenced by the underlying etiologies leading to decreased volumes. METHODS: We retrospectively evaluated patients with an available LA volume index (LAVI) as measured by echocardiography who came to our institution between 2011 and 2016. Individuals with small LA (LAVI < 16 ml/m2) were included and divided according to the etiology of the small LA (determined or indeterminate) and investigated according to the specific etiology. RESULTS: The cohort consisted of 288 patients with a mean age of 56 ± 18 years. An etiology for small LA was determined in 84% (n=242). The 1-year mortality rate of the entire cohort was 20.5%. Patients with indeterminate etiology (n=46) demonstrated a lower mortality rate compared with determined etiologies (8.7% vs. 22.7%, P = 0.031). However, following propensity score adjustments for baseline characteristics, there was no significant difference between the groups (P = 0.149). The only specific etiology independently associated with 1-year mortality was the presence of space occupying lesions (odds ratio 3.26, 95% confidence interval 1.02-10.39, P = 0.045). CONCLUSIONS: Small LA serve as a marker for negative outcomes, and even in cases of undetected etiology, the prognosis remains poor. The presence of small LA should alert the physician to a high risk of mortality, regardless of the underlying disease.

Percutaneous Cardiac Chambers and Pulmonary Artery Aspiration.

PURPOSE OF REVIEW: The clinical guidelines and current practice in the field of removable cardiovascular pathologies are not aligned and are in fluctuation. The purpose of this review manuscript is to propose adjustments and forecast changes in clinical practice in this field ahead of irrefutable evidence. Percutaneous aspiration devices may be used in case of pulmonary embolism, endocarditis, cardiac thrombi, and tumors. The rationale of treatment includes prevention of emboli, endocarditis debulking and modification, sampling of tissue, and salvage therapy. We are describing the contemporary treatments that are occurring in practice outside and above guidelines. RECENT FINDINGS: The current standard therapy for the above-mentioned entities is not supported by robust data. Moreover, evidence suggesting priority for the use of percutaneous aspiration devices as first-line therapy-before turning to or in lieu of surgery or thrombolysis-continues to accumulate. However, guidelines still mention percutaneous aspiration only as an alternative to standard treatment. In the current review, we discuss the pathophysiology that supports percutaneous cardiac and pulmonary artery aspiration, the commonly used devices for that purpose, their clinical evidence, and accordingly propose a modified approach to patient management. In addition, this review highlights fluid dynamic principles important in matter extraction in order to better define the utility of catheter-based technologies in different cardiovascular territories. The target diseases encompassed in this review are pulmonary embolism, cardiac masses, and vegetations.

Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing.

Background: We aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET). Methods: Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex. Results: One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction). Conclusions: Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics.

High neutrophil-to-lymphocyte ratio as an early sign of cardiotoxicity in breast cancer patients treated with anthracycline.

BACKGROUND: Cardiotoxicity, defined mainly as left ventricle (LV) dysfunction, is a significant side effect of anthracyclines (ANT) therapy. The need for an early simple marker to identify patients at risk is crucial. A high neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in cancer patients; however, its role as a predictor for cardiotoxicity development is unknown. OBJECTIVE: Evaluating whether elevated NLR, during ANT exposure, plays a predictive role in the development of cardiotoxicity as defined by LV global longitudinal strain (LV GLS) relative reduction (≥10%). METHODS AND RESULTS: Data were prospectively collected as part of the Israel Cardio-Oncology Registry. A total of 74 female patients with breast cancer, scheduled for ANT therapy were included. NLR levels were assessed at baseline (T1) and during ANT therapy (T2). All patients underwent serial echocardiography at baseline (T1) and after the completion of ANT therapy (T3). NLR ≥ 2.58 at T2 was found to be the optimal predictive cutoff for LV GLS deterioration. A relative LV GLS reduction ≥10% was significantly more common among patients with high NLR (50% vs. 20%, p = .009). NLR ≥ 2.58 at T2 increases the risk for LV GLS reduction by fourfold (odds ratio [OR]: 4.63, 95% confidence interval [CI]: 1.29-16.5, p = .02), with each increase of 1-point NLR adding an additional 15% risk (OR: 1.15, 95% CI: 1.01-1.32, p = .046). CONCLUSIONS: Our study provides novel data that high NLR levels, during ANT exposure, have an independent association with the development of LV dysfunction. Routine surveillance of NLR may be an effective means of risk-stratifying.

Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia.

Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model. We administered human recombinant IGF-1 or saline (control) in atherosclerotic FH pigs for 6 months. IGF-1 decreased relative coronary atheroma in vivo (intravascular ultrasound) and reduced lesion cross-sectional area (postmortem histology). IGF-1 increased plaque's fibrous cap thickness, and reduced necrotic core, macrophage content, and cell apoptosis, consistent with promotion of a stable plaque phenotype. IGF-1 reduced circulating triglycerides, markers of systemic oxidative stress, and CXCL12 chemokine levels. We used spatial transcriptomics (ST) to identify global transcriptome changes in advanced plaque compartments and to obtain mechanistic insights into IGF-1 effects. ST analysis showed that IGF-1 suppressed FOS/FOSB factors and gene expression of MMP9 and CXCL14 in plaque macrophages, suggesting possible involvement of these molecules in IGF-1's effect on atherosclerosis. Thus, IGF-1 reduced coronary plaque burden and promoted features of stable plaque in a pig model, providing support for consideration of clinical trials.

Sheathless Apical-Femoral Rail Technique for Transcatheter Aortic Valve Replacement - Case Report of a Difficult to Cross Stenosis.

A severely stenosed and calcified prosthetic aortic valve may be difficult to cross, on occasion even with only a wire. In the majority of cases eventually the valve will be crossed, but at a cost of prolonged fluoroscopy time, resulting in excessive exposure to radiation. It is therefore important to consider alternative techniques. The apical-femoral rail technique has been previously described. However, this technique involved establishing apical access, either surgically or percutaneously with a sheath. In the current case we describe a modified apical-femoral rail technique, performed sheathless with removal of the apical wire, allowing for spontaneous sealing.

Optimized definition of right ventricular dysfunction on computed tomography for risk stratification of pulmonary embolism.

OBJECTIVES: There is an ongoing discussion on the optimal right to left (RV/LV) diameter ratio threshold and the best definition of RV dysfunction on computed tomography pulmonary angiography (CTPA) for risk assessment of pulmonary embolism (PE). METHODS: On routine diagnostic CTPA, volumetric and diameter measurements (axial and reconstructed views) of the ventricles and reflux of contrast medium into the inferior vena cava (IVC) and hepatic veins were assessed in consecutive PE patients enrolled in a prospective single-center registry. In-hospital adverse outcome was defined as PE-related death, cardiopulmonary resuscitation, mechanical ventilation or catecholamine administration. RESULTS: Of 609 patients (median age, 69 [IQR, 56-77] years; 47 % male) included in the analysis, 68 patients (11.2 %) had an adverse outcome and 35 (5.7 %) died. While neither a RV/LV volume ratio ≥1.0 nor RV/LV diameter ratios ≥1.0 were able to predict an adverse outcome, higher thresholds increased specificity. Further, neither volumetric measurements nor reconstruction of images provided superior prognostic information compared to RV/LV ratios measured in axial planes. The combination of an axial RV/LV diameter ratio ≥1.5 with substantial reflux of contrast medium was present in 134 patients (22 %) and associated with the best prognostic performance to predict an adverse outcome in unselected (OR 3.7 [95 % CI, 2.0-6.6]) and normotensive (OR 2.8 [95 % CI, 1.1-6.7]) patients. CONCLUSION: A new definition of RV dysfunction (axial RV/LV diameter ratio ≥1.5 and substantial reflux of contrast medium to the IVC and hepatic veins) allows an optimized CTPA-based prediction of PE-related adverse outcome.

Evaluation of hemodynamically significant pericardial effusion by analysis of cardiac chambers volume by computed tomography.

OBJECTIVE: Pericardial effusion may present clinically as pleuritic chest pain, dyspnea, or hemodynamic compromise and is a frequent finding in computerized tomographic pulmonary angiography (CTPA) exams. We hypothesized that CTPA-based analysis of the cardiac chamber volumes can be used to predict the hemodynamic significance of pericardial effusion (HsPE) as compared with echocardiography. METHODS: Retrospective analysis of consecutive patients who underwent CTPA and echocardiography between January 2009 and November 2017 that ruled-out acute pulmonary embolism was included. Differences in cardiac chamber volumes were investigated in correlation to echocardiographic evidence of HsPE. RESULTS: The final cohort included 208 patients, of whom 22 (11%) were diagnosed with HsPE. The HsPE patients had much smaller right cardiac chamber volumes (Median 78.8 ml (IQR 72.4-89.1)) than patients without HsPE (Median 115.1 ml (IQR 87.4-150). A decision tree for the prediction of HsPE showed multiple cutoff values. Right atrium (RA) volume had the best accuracy (area under the curve 0.851, 95% confidence interval 0.776-0.925, p < .001) for predicting the presence of HsPE. An RA volume ≤86 ml yielded a sensitivity of 95.5%, a specificity of 64%, and a NPV of 99.2% for the presence of HsPE. CONCLUSION: CTPA-based volumetric information with focus on the RA volume may help predict the presence of HsPE. ADVANCES IN KNOWLEDGE: Pericardial effusion is a frequent finding in CTPA exams. Our study shows that CTPA-based volumetric information can predict the presence of HsPE with RA volume as the best indicator.