Combined Rotational excimer lASER coronary atherectomy (RASER) in non-crossable, non-dilatable coronary artery disease: observations from a single center.

BACKGROUND: Balloon non-crossable stenoses represent a challenging subset of coronary artery disease (CAD). They are clinically associated with patients who are older, frailer, and with multi-morbidities, and angiographically with increased tortuosity and coronary artery calcification. Combined rotational (RA) excimer laser coronary atherectomy (ELCA), or RASER, may facilitate stent delivery and deployment in non-crossable, non-dilatable severely calcified lesions. In this study, we assessed preliminary safety and efficacy of the RASER hybrid technique. METHODS: RASER feasible percutaneous coronary intervention (PCI) procedures performed at a large tertiary hospital in the northeast of England were retrospectively analyzed from September 1, 2008, to February 28, 2022. Major endpoints were in-hospital death from any cause, as well as procedural and angiographic success, defined by stent delivery with less than 50% residual stenosis and without clinical or angiographic complications, respectively. RESULTS: From 74 unique cases, there were 28 RASER, 24 ELCA/RA, 16 balloon angioplasty ± stenting, and 6 medically treated patients. In-hospital mortality rate was 5.2%, including 1 ELCA- and 3 RASER-treated patients. Successful stent delivery was achieved in significantly more RASER-treated patients compared to ELCA/RA- or balloon-treated patients: 96.4% (27/28), 25% (6/24), and 31.3% (5/16) respectively (P less than .001). CONCLUSIONS: In our retrospective, single-center study, patients with CAD who were deemed appropriate for RASER PCI had a high peri-procedural mortality rate. In this context, adjunctive RASER therapy provides acceptable safety and efficacy as a bailout strategy, with at least 3 out of 5 patients achieving satisfactory procedural and angiographic results. Randomized controlled trials are needed to comprehensively compare the clinical outcomes of high-risk RASER PCI vs conservative medical therapy.

Assessing heterogeneity on cardiovascular magnetic resonance imaging: a novel approach to diagnosis and risk stratification in cardiac diseases.

Cardiac disease affects the heart non-uniformly. Examples include focal septal or apical hypertrophy with reduced strain in hypertrophic cardiomyopathy, replacement fibrosis with akinesia in an infarct-related coronary artery territory, and a pattern of scarring in dilated cardiomyopathy. The detail and versatility of cardiovascular magnetic resonance (CMR) imaging mean it contains a wealth of information imperceptible to the naked eye and not captured by standard global measures. CMR-derived heterogeneity biomarkers could facilitate early diagnosis, better risk stratification, and a more comprehensive prediction of treatment response. Small cohort and case-control studies demonstrate the feasibility of proof-of-concept structural and functional heterogeneity measures. Detailed radiomic analyses of different CMR sequences using open-source software delineate unique voxel patterns as hallmarks of histopathological changes. Meanwhile, measures of dispersion applied to emerging CMR strain sequences describe variable longitudinal, circumferential, and radial function across the myocardium. Two of the most promising heterogeneity measures are the mean absolute deviation of regional standard deviations on native T1 and T2 and the standard deviation of time to maximum regional radial wall motion, termed the tissue synchronization index in a 16-segment left ventricle model. Real-world limitations include the non-standardization of CMR imaging protocols across different centres and the testing of large numbers of radiomic features in small, inadequately powered patient samples. We, therefore, propose a three-step roadmap to benchmark novel heterogeneity biomarkers, including defining normal reference ranges, statistical modelling against diagnosis and outcomes in large epidemiological studies, and finally, comprehensive internal and external validations.

Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Complex Coronary Artery Disease: Long-term Clinical Outcomes from a High-volume Center.

Background: Clinical equipoise between a percutaneous coronary intervention (PCI) and coronary artery bypass grafting surgery (CABG) in the treatment of complex coronary artery disease (CAD), including unprotected left main coronary artery (LMCA) and/or three-vessel disease (3VD), remains debatable. Methods: A retrospective analysis of an unselected cohort undergoing contemporary PCI versus CABG at a large center in 2015. Patients who received nonemergent treatment of unprotected LMCA and/or 3VD were included. The primary study endpoint was all-cause mortality at 5 years. Secondary endpoints included a composite of all-cause mortality, spontaneous myocardial infarction (MI), or ischemia-driven repeat revascularization at 30 days and 1 year. Results: Four hundred and thirty patients met the inclusion criteria, 225 had PCI, and 205 had CABG. PCI patients were older with frequent LMCA involvement and higher EuroSCORE yet they had a fourfold shorter in-hospital stay compared to CABG patients. At 5 years, there was no significant difference in the primary endpoint between CABG and PCI (adjusted Hazard ratios 0.68, 95% confidence interval: 0.38-1.22, P = 0.19). Likewise, there was no significant difference in the incidence of the secondary composite endpoint or its components at 30 days or 1 year. A propensity score-matched analysis in 220 patients revealed similar outcomes. Conclusions: In real-world long-term contemporary data, survival after PCI was comparable to CABG at 5 years in patients with unprotected LMCA and/or 3VD. At 1 year, the incidence of spontaneous MI and ischemia-driven repeat revascularization did not differ between the two cohorts. The mode of revascularization in these complex patients should be guided by the heart team.

Early experience of intravascular lithotripsy in unprotected calcified left main coronary artery disease.

BACKGROUND: Treatment of unprotected severely calcified left main coronary artery (LMCA) disease is a complex interventional procedure. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are safe and effective methods of treating coronary calcification in the non-LMCA setting. This retrospective analysis assessed the feasibility of IVL versus RA in unprotected LMCA disease. METHODS: We analyzed IVL and RA procedures performed at a large tertiary hospital in the Northeast of England from January 1, 2019 to April 31, 2022. Major safety and efficacy endpoints were procedural and angiographic success, defined by stent delivery with <50 % residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of major adverse cardiac events (MACE) at 1 year. RESULTS: From 242 patients, 44 had LMCA IVL, 81 had LMCA RA and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4 % LMCA and 92.2 % non-LMCA cases. Procedural and angiographic success rates were ≥ 84 % across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases arrhythmias and cardiac tamponade complicated the procedures respectively. At 1 year, MACE occurred in 10/44 (22.7 %) LMCA IVL, 16/81 (19.8 %) LMCA RA and 25/117 (21.4 %) cases (p > 0.05). CONCLUSION: In our single center retrospective analysis, IVL is feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials.

Heart failure in patients with COPD exacerbations: Looking below the tip of the iceberg.

BACKGROUND: Patients surviving hospitalization for exacerbations of chronic obstructive pulmonary disease (ECOPD) are at heightened risk of cardiovascular events. Heart failure is often underdiagnosed and undertreated in COPD; better care could improve outcome. We aimed to capture contemporary investigation and management of heart failure (HF) in patients hospitalized with ECOPD. METHODS: In two UK hospitals, patients admitted with ECOPD between 2017 and 2020 were retrospectively identified. Baseline characteristics between known, newly diagnosed and no HF were compared using analysis of variance and chi-squared test. Impact of HF on mortality was assessed by Kaplan-Meier analysis and Cox proportional-hazards regression. Sensitivity and specificity of NT-proBNP for diagnosing HF at recognized thresholds were reported. RESULTS: On admission, 94/476 (19.7%) patients had known HF. Among remaining patients, 89/382 (23.3%) were investigated within 100 days of admission, confirming HF in 38. Of 33 patients with heart failure with reduced ejection fraction (HFrEF), 18 (54.5%) were prescribed ACE-inhibitor and B-blocker. 77/132 patients (58.3%) with HF and 108/344 patients (31.4%) without HF died (adjusted HR 2.03, 95% CI 1.46-2.82, p < 0.001) during follow up (median 11.7 months). At ≥400 pg/mL, NPV and PPV of NT-proBNP for the diagnosis of HF were 77.8% and 82.8%. CONCLUSIONS: A new diagnosis of HF was made in over 40% investigated. In patients with coexistent HF, undertreatment was common and 1-year mortality exceeded 50%. NT-proBNP may help identify patients who need cardiovascular functional imaging. Research to improve HF diagnosis and treatment in hospitalized ECOPD is urgently needed.

Target heart rate in heart failure with reduced ejection fraction and atrial fibrillation: Goldilocks zone.

The rates of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) continue to grow with many patients suffering from their combined impact on quality of life and prognosis. A lower heart rate (HR) in HFrEF is associated with reduced morbidity and mortality due to beta-blocker and ivabradine therapy. Postulated mechanisms include reduced neurohumoral activation, increased diastolic filling time and myocardial energy conservation. In contrast, the landmark randomised controlled non-inferiority RACE II trial demonstrated that a lenient rate control strategy (target HR <110 beats per minute [bpm]) was more attainable and safer than a strict rate control strategy (resting HR <80 bpm) in permanent AF. Physiologically, a higher HR is needed to compensate for the lost 'atrial kick' that contributes to the cardiac output by coordinated atrial contractions in normal sinus rhythm. This leaves the not insignificant number of patients with HFrEF and AF in a conundrum over optimal HR control. Retrospective analyses of AF and HR control in landmark HFrEF trials (e.g. CHARM, PARADIGM and ATMOSPHERE) point towards better outcomes with a less stringent target HR. However, this association disappears after adjustment for known prognostic markers in HFrEF, including left ventricular ejection fraction, New York Heart Association class and NT-proBNP levels. There is a clear need for dedicated randomised controlled trials, investigating rate control strategies in this increasingly large subgroup of patients. Regardless of rate control strategy, effective anti-coagulation and guideline-directed medical therapy must not be forgotten in the treatment of patients with HFrEF and AF.

High-Sensitivity Cardiac Troponin I and Clinical Risk Scores in Patients With Suspected Acute Coronary Syndrome.

BACKGROUND: High-sensitivity cardiac troponin assays can help to identify patients who are at low risk of myocardial infarction in the emergency department. We aimed to determine whether the addition of clinical risk scores would improve the safety of early rule-out pathways for myocardial infarction. METHODS: In 1935 patients with suspected acute coronary syndrome, we evaluated the safety and efficacy of 2 rule-out pathways alone or in conjunction with low-risk TIMI (Thrombolysis In Myocardial Infarction) (0 or 1), GRACE (Global Registry of Acute Coronary Events) (≤108), EDACS (Emergency Department Assessment of Chest Pain Score) (<16), or HEART (History, ECG, Age, Risk factors, Troponin) (≤3) scores. The European Society of Cardiology 3-hour pathway uses a single diagnostic threshold (99th percentile), whereas the High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) pathway applies different thresholds to rule out (<5 ng/L) and rule in (>99th percentile) myocardial infarction. RESULTS: Myocardial infarction or cardiac death during the index presentation or at 30 days occurred in 14.3% of patients (276/1935). The European Society of Cardiology pathway ruled out 70%, with 27 missed events giving a negative predictive value of 97.9% (95% CI, 97.1-98.6). The addition of a HEART score ≤3 reduced the proportion ruled out by the European Society of Cardiology pathway to 25% but improved the negative predictive value to 99.7% (95% CI, 99.0-100; P<0.001). The High-STEACS pathway ruled out 65%, with 3 missed events for a negative predictive value of 99.7% (95% CI, 99.4-99.9). No risk score improved the negative predictive value of the High-STEACS pathways, but all reduced the proportion ruled out (24% to 47%; P<0.001 for all). CONCLUSIONS: Clinical risk scores significantly improved the safety of the European Society of Cardiology 3-hour pathway, which relies on a single cardiac troponin threshold at the 99th percentile to rule in and rule out myocardial infarction. Where lower thresholds are used to rule out myocardial infarction, as applied in the High-STEACS pathway, risk scores halve the proportion of patients ruled out without improving safety. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01852123.

Online Tool to Improve Stratification of Adverse Events in Stroke Clinical Trials.

BACKGROUND AND PURPOSE: Knowing characteristic adverse events (AEs) and their incidence among patients participating in acute stroke trials may assist interpretation of future studies. We aimed to develop an online tool to inform stroke trial safety. METHODS: We identified relevant AEs from patients within the Virtual International Stroke Trials Archive (VISTA), using receiver operating characteristic principles. We modeled their incidence on patient age, baseline National Institutes of Health Stroke Scale, and comorbidities using binary logistic regression. Models with an R(2) >5% were deemed powerful enough to predict expected AE incidences and were included. The calculator was developed using programs R and Visual Studios. RESULTS: Forty-eight of the most common AEs were identified and incorporated into the IschAEmic Stroke Calculator. The calculator, publicly available at http://www.vistacollaboration.org calculates the expected incidence of AEs or groups of AEs in a trial cohort and where possible compares them with the observed incidence. CONCLUSIONS: The IschAEmic Stroke Calculator is an open access resource to support safety interpretation within acute stroke trials. Prediction of AEs with higher likelihood of occurrence may direct preventive clinical measures.

Expanded criteria donor and donation after circulatory death renal allografts in the West of Scotland: Their place in the kidney allocation process.

INTRODUCTION: Due to the rising disparity between demand and availability, organs from expanded criteria donors (ECD) and donors after determination of circulatory death (DCD) are increasingly used. The purpose of this study was to report outcomes in recipients of ECD and DCD renal allografts from a single centre. METHODS: A retrospective analysis from a single centre for all renal transplants performed between 2001 and 2010 inclusive was undertaken. SCD (standard criteria donor) and ECD organs were compared, as were DCD and DBD (donation after determination of brain stem death) organs. Baseline data and predefined standard transplant outcomes were collected and compared using appropriate statistical tests. P < 0.05 was defined as significant. RESULTS: 729 renal transplants were performed. Comparing ECD to SCD organs, there was a significant difference in graft survival between groups (logrank for trend, p = 0.032) with ECD organs doing worse than SCD organs. Short-term outcomes showed a similar disparity with a higher 1-year post-transplant creatinine and delayed graft function (DGF) rate in ECD grafts. Nevertheless, outcomes were still clinically acceptable. When comparing DCD to DBD organs, no such differences were apparent, with DCD organs appearing to perform at least as well as DBD organs. In our cohort, unlike some previous studies, DGF rates were similar in both DCD and DBD groups. CONCLUSIONS: Although ECD organs perform less well than SCD organs, outcomes are still acceptable and our results support their continuing use. When considering DCD organs, our data support the view that they should no longer be necessarily regarded as marginal grafts. Our low DGF rates are perhaps explained by local factors contributing to a short CIT.

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials.

BACKGROUND AND PURPOSE: Adverse events (AE) in trial populations present a major burden to researchers and patients, yet most events are unrelated to investigational treatment. We aimed to develop a coherent list of expected AEs, whose incidence can be predicted by patient characteristics that will inform future trials and perhaps general poststroke care. METHODS: We analyzed raw AE data from patients participating in acute ischemic stroke trials. We identified events that occurred with a lower 99% confidence bound greater than nil. Among these, we applied receiver operating characteristic principles to select the fewest types of events that together represented the greatest number of reports. Using ordinal logistic regression, we modeled the incidence of these events as a function of patient age, sex, baseline National Institutes of Health Stroke Scale, and multimorbidity status, defining P<0.05 as statistically significant. RESULTS: We analyzed 5775 placebo-treated patients, reporting 21 217 AEs. Among 756 types of AEs, 132 accounted for 82.7%, of which 80% began within 10 days after stroke. Right hemisphere (odds ratio [OR], 1.67), increasing baseline National Institutes of Health Stroke Scale (OR, 1.11), multimorbidity status (OR, 1.09 per disease), patient age (OR, 1.01 per year), height (OR, 1.01 per centimeter), diastolic blood pressure (OR, 0.99 per mm Hg), and smoking (OR, 0.82) were independently associated with developing more AEs but together explained only 13% of the variation. CONCLUSIONS: A list of 132 expected AEs after acute ischemic stroke may be used to simplify interpretation and reporting of complications. AEs can be modestly predicted by patient characteristics, facilitating stratification of patients by risk for poststroke complications.