Cause and preventability of in-hospital mortality after PCI: A statewide root-cause analysis of 1,163 deaths.

BACKGROUND: Mortality is the most devastating complication of percutaneous coronary interventions (PCI). Identifying the most common causes and mechanisms of death after PCI in contemporary practice is an important step in further reducing periprocedural mortality. OBJECTIVES: To systematically analyze the cause and circumstances of in-hospital mortality in a large, multi-center, statewide cohort. METHODS: In-hospital deaths after PCI occurring at 39 hospitals included in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) between 2012 and 2014 were retrospectively reviewed using validated methods. A priori PCI-related mortality risk was estimated using the validated BMC2 model. RESULTS: A total of 1,163 deaths after PCI were included in the study. Mean age was 71±13 years, and 507 (44%) were women. Left ventricular failure was the most common cause of death (52% of cases). The circumstance of death was most commonly related to prior acute cardiovascular condition (61% of cases). Procedural complications were considered contributing to mortality in 235 (20%) cases. Death was rated as not preventable or slightly preventable in 1,045 (89.9%) cases. The majority of the deaths occurred in intermediate or high-risk patients, but 328 (28.2%) deaths occurred in low-risk patients (<5% predicted risk of mortality). PCI was considered rarely appropriate in 30% of preventable deaths. CONCLUSIONS: In-hospital mortality after PCI is rare, and primarily related to pre-existing critical acute cardiovascular condition. However, approximately 10% of deaths were preventable. Further research is needed to characterize preventable deaths, in order to develop strategies to improve procedural safety.

Early reduction in cardiorespiratory fitness and diastolic reserve following radiation therapy for lung cancer.

BACKGROUND: Contemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy. METHODS: Ten patients (69 [61-76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO2peak], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured. RESULTS: The VO2peak was reduced at baseline (1.245 [0.882-1.605] L·min- 1; 70 [62-86] %-predicted) and significantly declined (1.095 [0.810-1.448] L·min- 1, P = 0.047; 62 [56-76] %-predicted, P = 0.005) at 6.0 [3.0-6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27-1.88] to 1.57 [1.12-1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56-65]% to 66 [57-68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7-41.6] vs. 12.8 [3.1-35.9]). The hsCRP increased significantly from 4.4 [1.4-5.8] to 6.1 [3.7-20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49-125] to 121 [88-191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8-25] to 15.5 [11.5-20]; P = 0.021) post-radiotherapy. CONCLUSIONS: Patients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO2peak, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).

Mechanical Circulatory Support for High-Risk Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: This review will focus on the indications of mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (PCI) and then analyze in detail all MCS devices available to the operator, evaluating their mechanisms of action, pros and cons, contraindications, and clinical data supporting their use. RECENT FINDINGS: Over the last decade, the interventional cardiology arena has witnessed an increase in the complexity profile of the patients and lesions treated in the catheterization laboratory. Patients with significant comorbidity burden, left ventricular dysfunction, impaired hemodynamics, and/or complex coronary anatomy often cannot tolerate extensive percutaneous revascularization. Therefore, a variety of MCS devices have been developed and adopted for high-risk PCI. Despite the variety of MCS available to date, a detailed characterization of the patient requiring MCS is still lacking. A precise selection of patients who can benefit from MCS support during high-risk PCI and the choice of the most appropriate MCS device in each case are imperative to provide extensive revascularization and improve patient outcomes. Several new devices are being tested in early feasibility studies and randomized clinical trials and the experience gained in this context will allow us to provide precise answers to these questions in the coming years.

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1.

BACKGROUND: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs). METHODS: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin-1" and "treatment." RESULTS: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine-rich repeat and pyrin-domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL-1ß, the prototypical pro-inflammatory cytokine involved in CVDs. Other pro-inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL-1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome. CONCLUSION: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies.

Impact of C-reactive protein levels and role of anakinra in patients with ST-elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). The effectiveness of anakinra according to the degree of systemic inflammation in STEMI has not been addressed. METHODS: We analyzed 139 patients from three Virginia Commonwealth University Anakinra Response Trial randomized clinical trials to assess whether CRP levels predicted HF hospitalization or death in patients with STEMI, and if CRP levels influenced the effects of treatment with anakinra. RESULTS: CRP cut-off levels for prediction of the composite of death or HF hospitalization for CRP at admission, 3 and 14 days were, respectively 6.45 mg/L (100% of sensitivity and 66.1% specificity), 26 mg/L (100% of sensitivity and 78% specificity) and 9.56 mg/L (100% of sensitivity and 80% specificity). More patients with elevated CRP levels died or had a HF hospitalization (5/47 [11%] vs 0/82 [0%], p = 0.004 for CRP at admission; 5/32 [15.6%] vs 0/92 [0%], p < 0.001 for day 3 and 5/26 [19%] vs 0/89 [0%], p < 0.001 for day 14). A greater number of patients treated with anakinra had low CRP levels at 3 and 14 days compared to placebo (Odds Ratio 0.11 [95% IC 0.04-0.28], p < 0.0001 and OR 0.35 [95% CI 0.14-0.86], p = 0.02, respectively). Anakinra significantly prevented death or HF hospitalization in patients with high inflammatory burden (p = 0.04 for admission, p = 0.24 for day 3, and p = 0.05 for day 14). CONCLUSION: Patients with elevated CRP had higher incidence of HF hospitalization or death. Anakinra reduced the number of patients with elevated CRP levels and prevented death or HF hospitalization in patients with elevated CRP levels.

Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra. METHODS: We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials. RESULTS: We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05). CONCLUSIONS: Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

Characterisation of coronary microvascular dysfunction in patients with severe aortic stenosis undergoing TAVI.

BACKGROUND: Microvascular resistance reserve (MRR) is a validated measure of coronary microvascular function independent of epicardial resistances. AIMS: We sought to assess whether MRR is associated with adverse cardiac remodelling, a low-flow phenotype and extravalvular cardiac damage (EVCD) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS: Invasive thermodilution-based assessment of the coronary microvascular function of the left anterior descending artery was performed in a prospective, multicentre cohort of patients undergoing TAVI. Coronary microvascular dysfunction (CMD) was defined as the lowest MRR tertile of the study cohort. Haemodynamic measurements were performed at baseline and then repeated immediately after TAVI. EVCD and markers of a low-flow phenotype were assessed with echocardiography. RESULTS: A total of 134 patients were included in this study. Patients with low MRR were more frequently females, had a lower estimated glomerular filtration rate and a higher rate of atrial fibrillation. MRR was significantly lower in patients with advanced EVCD (median 1.80 [1.26-3.30] vs 2.50 [1.87-3.41]; p=0.038) and in low-flow, low-gradient AS (LF LG-AS) (median 1.85 [1.20-3.04] vs 2.50 [1.87-3.40]; p=0.008). Overall, coronary microvascular function tended to improve after TAVI and, in particular, MRR increased significantly after TAVI in the subgroup with low MRR at baseline. However, MRR was significantly impaired in 38 (28.4%) patients immediately after TAVI. Advanced EVCD (adjusted odds ratio 3.08 [1.22-7.76]; p=0.017) and a low-flow phenotype (adjusted odds ratio 3.36 [1.08-10.47]; p=0.036) were significant predictors of CMD. CONCLUSIONS: In this observational, hypothesis-generating study, CMD was associated with extravalvular cardiac damage and a low-flow phenotype in patients with severe AS undergoing TAVI.

Valve-in-valve transcatheter aortic valve implantation: The issues behind crossing a bioprosthesis.

Valve-in-valve transcatheter aortic valve implantation (ViV TAVI) is rapidly arising as a safe and effective alternative to redo-surgery in the treatment of bioprostheses deterioration. While scientific community is currently focusing its attention on the most common limitations related to this procedure, such as the risk of coronary obstruction and patient-prosthesis mismatch, data regarding the first step of a ViV TAVI, the crossing of a degenerated bioprosthesis, are still lacking. The aim of this review is to analyze the available information about bioprosthesis crossing, to show the inherent challenges encountered by interventional cardiologists during valve crossing and to describe the current strategies to perform a correct crossing.

IL-1 blockade in cardiovascular disease: an appraisal of the evidence across different inflammatory paradigms.

Pre-clinical and clinical studies suggest a role for inflammation in the pathophysiology of cardiovascular (CV) diseases. The NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is activated during tissue injury and releases interleukin-1ß (IL-1ß). We describe three paradigms in which the NLRP3 inflammasome and IL-1ß contribute to CV diseases. During acute myocardial infarction (AMI), necrotic cell debris, including IL-1α, induce NLRP3 inflammasome activation and further damage the myocardium contributing to heart failure (HF) (acute injury paradigm). In chronic HF, IL-1ß is induced by persistent myocardial overload and injury, neurohumoral activation and systemic comorbidities favoring infiltration and activation of immune cells into the myocardium, microvascular inflammation, and a pro-fibrotic response (chronic inflammation paradigm). In recurrent pericarditis, an autoinflammatory response triggered by cell injury and maintained by the NLRP3 inflammasome/IL-1ß axis is present (autoinflammatory disease paradigm). Anakinra, recombinant IL-1 receptor antagonist, inhibits the acute inflammatory response in patients with ST elevation myocardial infarction (STEMI) and acute HF. Canakinumab, IL-1ß antibody, blunts systemic inflammation and prevents complications of atherosclerosis in stable patients with prior AMI. In chronic HF, anakinra reduces systemic inflammation and improves cardiorespiratory fitness. In recurrent pericarditis, anakinra and rilonacept, a soluble IL-1 receptor chimeric fusion protein blocking IL-1α and IL-1ß, treat and prevent acute flares. In conclusion, the NLRP3 inflammasome and IL-1 contribute to the pathophysiology of CV diseases, and IL-1 blockade is beneficial with different roles in the acute injury, chronic inflammation and autoinflammatory disease paradigms. Further research is needed to guide the optimal use of IL-1 blockers in clinical practice.

Comparative evaluation of intracardiac, transesophageal, and transthoracic echocardiography in the assessment of patent foramen ovale: A retrospective single-center study.

INTRODUCTION: Certain patent foramen ovale (PFO) characteristics, such as a large right-to-left shunt (RLS) or atrial septal aneurysm, identify patients who may receive the highest clinical benefit from percutaneous PFO closure. This study aimed to compare intracardiac echocardiography (ICE) with standard echocardiographic imaging in the evaluation of high-risk PFO characteristics and RLS severity in patients with PFO-associated stroke. METHODS: We conducted a retrospective review of all patients aged ≥18 years who underwent percutaneous PFO closure for PFO-associated stroke and received all three ultrasound-based cardiac imaging modalities and had interpretable results (N = 51). We then compared RLS severity, high-risk PFO characteristics, and the proportion of patients with a higher likelihood of PFO-associated stroke by ICE versus transthoracic echocardiogram (TTE) and transesophageal echocardiogram (TEE). RESULTS: The final cohort had a mean (±SE) age of 48.4 (±1.8) years and was predominantly female (58.8%). ICE was more likely to identify a large RLS versus TTE/TEE combined (66.7% vs. 45.1%; p = 0.03). The use of ICE resulted in significantly more patients being reclassified as having a higher likelihood of PFO-associated stroke (TTE vs. TEE vs. ICE: 10.4% vs. 14.6% vs. 25%; p = 0.03). A high-quality bubble study was found to be the single most important factor associated with identifying a larger RLS across all modalities (ρ [p]; TTE: 0.49 [<0.001], TEE: 0.60 [<0.001], ICE: 0.32 [0.02]). The presence of a hypermobile septum was associated with significantly greater RLS on ICE (ρ [p]: 0.3 [0.03]), especially with poor quality bubble studies (ρ [p]: 0.49 [0.02]). CONCLUSION: In this observational study of patients with PFO-associated stroke, ICE detected a large RLS more frequently than TTE and TEE; and reclassified some patients as having a higher likelihood of PFO-associated stroke.

Interleukin-1 blockade in heart failure: an on-treatment and off-treatment cardiorespiratory fitness analysis.

AIMS: Interleukin-1 (IL-1) blockade may improve exercise capacity in patients with heart failure (HF) patients. The extent of the improvement and its persistence beyond discontinuation of IL-1 blockade is unknown. METHODS AND RESULTS: The primary objective was to determine changes in cardiorespiratory fitness and cardiac function on-treatment with IL-1 blocker, anakinra, and off-treatment, after treatment cessation. We performed cardiopulmonary exercise testing, Doppler echocardiography, and biomarkers in 73 patients with HF, 37 (51%) females, 52 (71%) Black-African-American, before and after treatment with anakinra 100 mg daily. In a subset of 46 patients, testing was also repeated after treatment cessation. Quality of life was assessed in each patient using standardized questionnaires. Data are presented as median and interquartile range. Treatment with anakinra for 4 [2-12] weeks was associated with a significant improvement in high-sensitivity C-reactive protein (from 6.2 [3.3-15.4] to 1.4 [0.8-3.4] mg/L, P < 0.001), peak oxygen consumption (VO2peak , from 13.9 [11.6-16.6] to 15.2 [12.9-17.4] mL/kg/min, P < 0.001). Ventilatory efficiency, exercise time, Doppler-derived signs and biomarkers of elevated intracardiac pressures, and quality-of-life measures also improved with anakinra. In the 46 patients in whom off-treatment data were available 12 [4-12] weeks later, many of the favourable changes seen with anakinra were largely reversed (from 1.5 [1.0-3.4] to 5.9 [1.8-13.1], P = 0.001 for C-reactive protein, and from 16.2 [14.0-18.4] to 14.9 [11.5-17.8] mL/kg/min, P = 0.017, for VO2peak ). CONCLUSIONS: These data validate IL-1 as an active and dynamic modulator of cardiac function and cardiorespiratory fitness in HF.

Duodenocaval fistula after bevacizumab therapy: case presentation and complete overview of the literature.

Duodenocaval fistula (DCF) is a very rare condition and is associated with a 41.1% of mortality rate. Although ingested foreign bodies, peptic ulcer disease and radiotherapy are often the etiologies described, only three patients have been described who developed DCF after bevacizumab therapy. We report a case of a 58-year-old woman with a history of ovarian neoplasia and subsequent surgical treatments, adjuvant radiotherapy and chemotherapy with bevacizumab with the appearance of a spontaneous DCF after 6 months at the end of this therapy. The multidisciplinary approach between oncologist and vascular surgeon together with the support of the anesthesiology team allowed the DFC to be treated surgically through the suture of the inferior vena cava and the duodenal breach. The patient was discharged on the 14th postoperative day and we found no postoperative morbidities both immediately and after 30 and 60 days.

Mitral valve remodeling in the development of obstructive hypertrophic cardiomyopathy.

Approximately 2/3 of patients with hypertrophic cardiomyopathy (HCM) have significant left ventricular outflow tract obstruction (LVOTO), which is caused by the interaction mitral valve apparatus and the hypertrophied septum. The contribution of mitral valve remodeling to the development of obstruction over time has never been described. We analyzed retrospectively 40 patients with HCM and no baseline obstruction followed up for a median of 2179 days. At follow up, 13 patients developed significant LVOTO. Patients who developed LVOTO had longer posterior leaflets and longer anterior leaflet residual length.

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra.

BACKGROUND: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). METHODS: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. RESULTS: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO2·kg-1·min-1, p = 0.015). CONCLUSION: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.