Proximal optimization technique and percutaneous coronary intervention for left main disease: POTENTIAL-LM.

BACKGROUND: Optimal stent deployment in left main (LM) bifurcation is paramount, and incomplete stent apposition may cause major adverse cardiac events (MACE). Bench studies show that the proximal optimization technique (POT) provides the best stent apposition. AIMS: We aimed to investigate the impact of POT on clinical outcomes in patients treated for unprotected LM (ULM) disease at our institution. METHODS: We identified 162 patients who underwent percutaneous coronary intervention (PCI) for ULM coronary disease in the Cardio-FR database. Out of these, 99 (61%) had undergone POT, while 63 patients were treated without POT. The primary outcome was the bifurcation-oriented composite endpoint (BOCE) of cardiac death, target-bifurcation myocardial infarction and target-bifurcation revascularization at maximal follow-up. RESULTS: Mean age was 76 years, and 69% presented with acute coronary syndrome. Mean follow-up was 2.25 years (822 days). The BOCE occurred in 43 (27%) of which 20 (20%) in the POT group and 23 (37%) in the no-POT group (p = 0.009). Cardiac death occurred in 15 (15%) patients in the POT- and 17 (27%) in no-POT group (p = 0.26). Target bifurcation revascularization occurred in 4 (4%) patients in the POT- and 6 (10%) patients in the no-POT group (p = 0.19). POT In the multivariate analysis, POT was the strongest parameter and was associated with BOCE, cardiac death, occurrence of any revascularization and all-cause mortality. CONCLUSION: The POT improves clinical outcomes. These findings strongly support the systematic use of POT in patients undergoing ULM-PCI.

Blood Flow Energy Identifies Coronary Lesions Culprit of Future Myocardial Infarction.

The present study establishes a link between blood flow energy transformations in coronary atherosclerotic lesions and clinical outcomes. The predictive capacity for future myocardial infarction (MI) was compared with that of established quantitative coronary angiography (QCA)-derived predictors. Angiography-based computational fluid dynamics (CFD) simulations were performed on 80 human coronary lesions culprit of MI within 5 years and 108 non-culprit lesions for future MI. Blood flow energy transformations were assessed in the converging flow segment of the lesion as ratios of kinetic and rotational energy values (KER and RER, respectively) at the QCA-identified minimum lumen area and proximal lesion sections. The anatomical and functional lesion severity were evaluated with QCA to derive percentage area stenosis (%AS), vessel fractional flow reserve (vFFR), and translesional vFFR (ΔvFFR). Wall shear stress profiles were investigated in terms of topological shear variation index (TSVI). KER and RER predicted MI at 5 years (AUC = 0.73, 95% CI 0.65-0.80, and AUC = 0.76, 95% CI 0.70-0.83, respectively; p < 0.0001 for both). The predictive capacity for future MI of KER and RER was significantly stronger than vFFR (p = 0.0391 and p = 0.0045, respectively). RER predictive capacity was significantly stronger than %AS and ΔvFFR (p = 0.0041 and p = 0.0059, respectively). The predictive capacity for future MI of KER and RER did not differ significantly from TSVI. Blood flow kinetic and rotational energy transformations were significant predictors for MI at 5 years (p < 0.0001). The findings of this study support the hypothesis of a biomechanical contribution to the process of plaque destabilization/rupture leading to MI.

Case Report: Double chimney in valve-in-valve procedures for high-risk coronary obstruction.

The chimney technique has been utilized to minimize the risk of coronary artery obstruction during valve-in-valve procedures. Here, we present a case involving an 89-year-old female patient with low coronary ostia, severe aortic regurgitation, and intractable heart decompensation caused by degenerated aortic bioprosthesis. The patient underwent a successful transcatheter aortic valve implantation procedure using the chimney technique in both coronary ostia.

Effects of SARS-COV-2 infection on outcomes in patients hospitalized for acute cardiac conditions. A prospective, multicenter cohort study (Swiss Cardiovascular SARS-CoV-2 Consortium).

Background: Although the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) causing coronavirus disease 2019 (COVID-19) primarily affects the respiratory system, the disease entity has been associated with cardiovascular complications. This study sought to assess the effect of concomitant SARS-COV-2 infection on clinical outcomes of patients hospitalized primarily for acute cardiac conditions on cardiology wards in Switzerland. Methods: In this prospective, observational study conducted in 5 Swiss cardiology centers during the COVID-19 pandemic, patients hospitalized due to acute cardiac conditions underwent a reverse-transcriptase polymerase chain reaction test at the time of admission and were categorized as SARS-COV-2 positive (cases) or negative (controls). Patients hospitalized on cardiology wards underwent treatment for the principal acute cardiac condition according to local practice. Clinical outcomes were recorded in-hospital, at 30 days, and after 1 year and compared between cases and controls. To adjust for imbalanced baseline characteristics, a subgroup of patients derived by propensity matching was analyzed. Results: Between March 2020 and February 2022, 538 patients were enrolled including 122 cases and 416 controls. Mean age was 68.0 ± 14.7 years, and 75% were men. Compared with controls, SARS-COV-2-positive patients more commonly presented with acute heart failure (35% vs. 17%) or major arrhythmia (31% vs. 9%), but less commonly with acute coronary syndrome (26% vs. 53%) or severe aortic stenosis (4% vs. 18%). Mortality was significantly higher in cases vs. controls in-hospital (16% vs. 1%), at 30 days (19.0% vs. 2.2%), and at 1 year (28.7% vs. 7.6%: p < 0.001 for all); this was driven primarily (up to 30 days) and exclusively (at one-year follow-up) by higher non-cardiovascular mortality, and was accompanied by a greater incidence of worsening renal function in cases vs. controls. These findings were maintained in a propensity-matched subgroup of 186 patients (93 cases and 93 controls) with balanced clinical presentation and baseline characteristics. Conclusions: In this observational study of patients hospitalized for acute cardiac conditions, SARS-COV-2 infection at index hospitalization was associated with markedly higher all-cause and non-cardiovascular mortality throughout one-year follow-up. These findings highlight the need for effective, multifaceted management of both cardiac and non-cardiac morbidities and prolonged surveillance in patients with acute cardiac conditions complicated by SARS-COV-2 infection.

Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial.

BACKGROUND: Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain. METHODS: BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310. FINDINGS: Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988). INTERPRETATION: In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation. FUNDING: Biotronik.

Abbreviated or Standard Antiplatelet Therapy in HBR Patients: Final 15-Month Results of the MASTER-DAPT Trial.

BACKGROUND: Clinical outcomes and treatment selection after completing the randomized phase of modern trials, investigating antiplatelet therapy (APT) after percutaneous coronary intervention (PCI), are unknown. OBJECTIVES: The authors sought to investigate cumulative 15-month and 12-to-15-month outcomes after PCI during routine care in the MASTER DAPT trial. METHODS: The MASTER DAPT trial randomized 4,579 high bleeding risk patients to abbreviated (n = 2,295) or standard (n = 2,284) APT regimens. Coprimary outcomes were net adverse clinical outcomes (NACE) (all-cause death, myocardial infarction, stroke, and BARC 3 or 5 bleeding); major adverse cardiac and cerebral events (MACCE) (all-cause death, myocardial infarction, and stroke); and BARC type 2, 3, or 5 bleeding. RESULTS: At 15 months, prior allocation to a standard APT regimen was associated with greater use of intensified APT; NACE and MACCE did not differ between abbreviated vs standard APT (HR: 0.92 [95% CI: 0.76-1.12]; P = 0.399 and HR: 0.94 [95% CI: 0.76-1.17]; P = 0.579; respectively), as during the routine care period (HR: 0.81 [95% CI: 0.50-1.30]; P = 0.387 and HR: 0.74 [95% CI: 0.43-1.26]; P = 0.268; respectively). BARC 2, 3, or 5 was lower with abbreviated APT at 15 months (HR: 0.68 [95% CI: 0.56-0.83]; P = 0.0001) and did not differ during the routine care period. The treatment effects during routine care were consistent with those observed within 12 months after PCI. CONCLUSIONS: At 15 months, NACE and MACCE did not differ in the 2 study groups, whereas the risk of major or clinically relevant nonmajor bleeding remained lower with abbreviated compared with standard APT. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

[Cardiac tumors in clinical practice]. / Les tumeurs cardiaques.

Cardiac tumors are rare in clinical practice but remain an essential part of the fast-growing field of cardio-oncology. They can be detected incidentally and consist of primary tumors (benign or malignant) and of the more prevalent secondary tumors (metastasis). They form a heterogeneous group of pathologies presenting with a wide panel of clinical symptoms according to their location and size. Multimodality cardiac imaging (echocardiography, CT, MRI and PET), in association with clinical and epidemiological factors, plays a key role in the diagnosis of cardiac tumors and a biopsy is therefore not systematically required. Treatment strategies for cardiac tumors vary depending on the malignancy and class of the tumor, but also consider associated symptoms, hemodynamic impact and embolic risk.

Les tumeurs cardiaques sont des pathologies rares mais elles ­appartiennent à un domaine en plein essor de la cardio-oncologie. Souvent découvertes fortuitement, elles comprennent les ­tumeurs cardiaques primaires (bénignes ou malignes) et, plus fréquemment, secondaires (métastases). Elles constituent un ­ensemble très hétérogène de pathologies, dont les manifestations cliniques varient en fonction de la taille et de la localisation. Le diagnostic repose sur une approche clinique, épidémiologique et plusieurs modalités d'imagerie (échocardiographie, CT, IRM et PET-CT), sans nécessité systématique de biopsie. La stratégie de traitement d'une tumeur cardiaque dépend de la symptomatologie du patient, du risque embolique ou hémodynamique lié à la masse, ainsi que de sa malignité.

Clinical outcomes after unprotected left main coronary artery occlusion: A retrospective multicentre cohort analysis.

AIMS: Unprotected left main coronary artery (ULMCA) occlusion is a rare and disastrous condition with scarce data on presentation and outcomes. Herein, we report data on patients presenting with acute coronary syndrome due to ULMCA occlusion at four different institutions. METHODS: This is an international multicentre observational study. Baseline characteristics were retro- and prospectively collected. Clinical follow-up was prospective. The primary outcome was in-hospital death. Patients surviving the index hospitalization were compared with nonsurvivors to find predictors of survival. RESULTS: The study population consisted of 55 patients. Eight patients (15%) died in the cath lab, and 23 (42%) died in hospital. Three (6%) deaths were noncardiac and due to major bleeding. Thirty-two (58%) patients survived the index hospitalization and were discharged. These patients were followed for a median of 17.5 months during which three cardiac deaths occurred. Repeat revascularization was performed in 25% (n = 8). Overall mortality at maximum follow-up was 47% (n = 26). The only significant predictor for hospital survival was left ventricular ejection fraction (odds ratio [OR]: 1.10 (per 1 point increase); 95% confidence interval [CI]: 1.02-1.19; p = 0.02). CONCLUSION: ULMCA occlusion carries a high short-term mortality. Patients who survive index hospitalization have similar mortality rates as compared with other st elevation myocardial infarction patients.

Deep learning-based prediction of future myocardial infarction using invasive coronary angiography: a feasibility study.

BACKGROUND: Angiographic parameters can facilitate the risk stratification of coronary lesions but remain insufficient in the prediction of future myocardial infarction (MI). AIMS: We compared the ability of humans, angiographic parameters and deep learning (DL) to predict the lesion that would be responsible for a future MI in a population of patients with non-significant CAD at baseline. METHODS: We retrospectively included patients who underwent invasive coronary angiography (ICA) for MI, in whom a previous angiogram had been performed within 5 years. The ability of human visual assessment, diameter stenosis, area stenosis, quantitative flow ratio (QFR) and DL to predict the future culprit lesion (FCL) was compared. RESULTS: In total, 746 cropped ICA images of FCL and non-culprit lesions (NCL) were analysed. Predictive models for each modality were developed in a training set before validation in a test set. DL exhibited the best predictive performance with an area under the curve of 0.81, compared with diameter stenosis (0.62, p=0.04), area stenosis (0.58, p=0.05) and QFR (0.67, p=0.13). DL exhibited a significant net reclassification improvement (NRI) compared with area stenosis (0.75, p=0.03) and QFR (0.95, p=0.01), and a positive nonsignificant NRI when compared with diameter stenosis. Among all models, DL demonstrated the highest accuracy (0.78) followed by QFR (0.70) and area stenosis (0.68). Predictions based on human visual assessment and diameter stenosis had the lowest accuracy (0.58). CONCLUSION: In this feasibility study, DL outperformed human visual assessment and established angiographic parameters in the prediction of FCLs. Larger studies are now required to confirm this finding.

[Wellens Syndrome: A rare entity not to be neglected]. / Syndrome de Wellens : une entité rare à ne pas méconnaître.

Wellens syndrome is a particular presentation of acute coronary syndrome which manifests, in a patient most often asymptomatic at the time of the examination, by specific electrocardiographic signs, in particular T waves in the precordial leads V2 and V3. The absence of chest pain at the time of the examination and the normality of cardiac enzymes can be falsely reassuring and constitute diagnostic pitfalls. This syndrome is associated with an often critical stenosis of the IVA (anterior descending artery). A good reading of the ECG is mandatory for the diagnosis. The management is done in interventional cardiology in order to avoid a massive anterior infarction.

Le syndrome de Wellens est une présentation particulière de syndrome coronarien aigu qui se manifeste chez un patient le plus souvent asymptomatique au moment de l'examen, par des signes électrocardiographiques spécifiques, notamment des ondes T dans les dérivations précordiales V2 et V3. L'absence de douleur thoracique et la normalité des enzymes cardiaques peuvent être faussement rassurantes et constituer des pièges diagnostiques. Ce syndrome est associé à une sténose souvent critique de l'IVA (artère interventriculaire antérieure). Une bonne lecture de l'ECG permet d'en faire le diagnostic. La prise en charge se fait en cardiologie interventionnelle afin d'éviter un infarctus antérieur massif.

Is the folk medicine known as "The Secret" efficient in reducing bleeding after percutaneous coronary procedures?: a double-blinded, randomised trial.

AIM: Percutaneous coronary interventions require an arterial approach and administration of antithrombotic drugs. This may lead to bleeding complications. The aim of this study was to test whether "The Secret" - a pagan prayer - is effective in reducing post-interventional bleeding. DESIGN: Randomised controlled trial. SETTING: Monocentric, tertiary care centre. PARTICIPANTS: From January to July 2022, 200 patients (aged >18 years) undergoing elective coronary angiography were included in the study. INTERVENTION: The intervention group received "The Secret" in addition to the normal procedure. The control group was treated according to standard practice. MAIN OUTCOME MEASURES: The primary outcome was the rate of in-hospital bleeding according to the Bleeding Academic Research Consortium (BARC) consensus definition. RESULTS: The rate of bleeding was similar in both groups ("The Secret" group vs control group) with 16% versus 14% (p=0.69) of BARC 1, 12% versus 13% (p=0.81) of BARC 2, and 0% versus 0% of BARC 3 and 5 (p=1.00). Most (76%) of the participants believed that "The Secret" would be efficient in preventing bleeding. CONCLUSIONS: This study demonstrates no effect on bleeding after percutaneous coronary procedures. A large majority of our study population believe that "The Secret" can have a positive effect on their hospital care.

Corrigendum: Yield of the electrophysiological study in patients with new-onset left bundle branch block after transcathether aortic valve replacement: The PR interval matters.

[This corrects the article DOI: 10.3389/fcvm.2022.910693.].

Treating Femoral Artery Pseudoaneurysm by Tumescence Anesthesia and Echo-Guided Compression Technique (TACT): Clinical Outcome in 82 Consecutive Patients.

PURPOSE: Pseudoaneurysm (PA) of the access artery is a common and potentially severe complication after percutaneous endovascular interventions. Most PA require interventional therapy, including thrombin injection, covered stent implantation, or surgical repair, which are costly and associated with other complications. Treating PA by external compression is uncomfortable and time consuming, with a low success rate. By injecting local tumescence anesthesia around the PA and close to its neck, the tumescence anesthesia and echo-guided compression technique (TACT) aims to improve efficacy and patient's comfort. MATERIALS AND METHODS: We retrospectively reviewed all consecutive patients treated for femoral PA in our center from May 2009 to July 2019 and estimated efficacy and safety. Vascular specialists performed TACT according to a standardized protocol including ultrasound-guided injection of tumescence solution (45 ml of 0.9% saline, 15 ml of lidocaine 1%/epinephrine 5 µg/ml) in the soft tissue around the PA and its neck, local compression with the sonography probe until PA closure, and external compression by elastic belt for 3 hours. RESULTS: Among a total of 125 patients with femoral artery PA, 82 (65.6%) were treated by TACT (including 3 patients with haemorrhagic shock), 14 (11.2%) by thrombin injection; 12 (9.6%) by endovascular interventions; 8 (6.4%) by open surgery; and 9 (7.2%) conservatively. In patients treated by TACT, PA neck was short (<1 cm) in 51.8% and mean cavity diameter 30 ± 23 mm. After injection of 58 ± 8 ml of tumescence solution, mean time of echo-guided compression was 12 ± 8 minutes. Pseudoaneurysm was successfully closed in 92.7% after the first attempt and in 96.3% after the second attempt. The intervention was well tolerated, without any adverse event. CONCLUSION: Tumescence anesthesia and echo-guided compression technique (TACT) is an effective and safe treatment for PA. Compared to other therapies, TACT is minimally invasive and widely available for minimal costs, even for large PA and in unstable patients. CLINICAL IMPACT: Tumescence anesthesia and echo-guided compression technique seems to be an efficient, safe, and a fair economical choice in comparison with alternative techniques. The implementation of this procedure is simple with low risk of complications. Based on the results of this study, we believe that TACT should be considered as the first-line treatment of most iatrogenic PA.

Yield of the electrophysiological study in patients with new-onset left bundle branch block after transcathether aortic valve replacement: The PR interval matters.

Background: Studies suggest that performing an electrophysiological study (EPS) may be useful to identify patients with new-onset left bundle branch block (LBBB) post-TAVR at risk of atrioventricular block. However, tools to optimize the yield of such strategy are needed. We therefore aimed to investigate whether 12-lead ECG changes post-TAVR may help identify patients with abnormal EPS findings. Materials and methods: Consecutive patients with new-onset LBBB post-TAVR who underwent EPS were included. PR and QRS intervals were measured on 12-lead ECG pre-TAVR and during EPS. Abnormal EPS was defined as an HV interval > 55 ms. Results: Among 61 patients, 28 (46%) had an HV interval > 55 ms after TAVR. Post-TAVR PR interval and ΔPR (PR-post-pre-TAVR) were significantly longer in patients with prolonged HV (PR: 188 ± 38 vs. 228 ± 34 ms, p < 0.001, ΔPR: 10 ± 30 vs. 34 ± 23 ms, p = 0.001), while no difference was found in QRS duration. PR and ΔPR intervals both effectively discriminated patients with HV > 55 ms (AUC = 0.804 and 0.769, respectively; p < 0.001). A PR > 200 ms identified patients with abnormal EPS results with a sensitivity of 89% and a negative predictive value (NPV) of 88%. ΔPR ≥ 20 ms alone provided a somewhat lower sensitivity (64%) but combining both criteria (i.e., PR > 200 ms or ΔPR ≥ 20 ms) identified almost every patients with abnormal HV (sensitivity = 96%, NPV = 95%). Selecting EPS candidate based on both criteria would avoid 1/3 of exams. Conclusion: PR interval assessment may be useful to select patients with new-onset LBBB after TAVR who may benefit most from an EPS. In patients with PR ≤ 200 ms and ΔPR < 20 ms the likelihood of abnormal EPS is very low independently of QRS changes.

Remote blood pressure monitoring with a wearable photoplethysmographic device in patients undergoing coronary angiography: the senbiosys substudy.

AIMS: The purpose of this study is to evaluate the accuracy of the Senbiosys device in measuring blood pressure (BP) by photoplethysmography (PPG) in patients undergoing coronary angiography. METHODS: This is a substudy within the Senbiosys trial, which is a prospective, single-arm, single-center study, evaluating the accuracy of BP estimation of the Senbiosys device compared to invasive BP. Patients referred for coronary angiography underwent invasive BP measurement and simultaneously wore the Senbiosys ring. SBP and DBP estimations measured by the Senbiosys device were compared with invasive measurements. RESULTS: A total of 25 patients were included. Overall, 708 epochs with adequate PPG signal belonging to 17 patients were analyzed. A total of 84% of the SBP estimates and 99% of the DBP estimates have an absolute error of less than 10 mmHg compared with the invasive measurements. Mean difference was 2.3 ± 7.0 mmHg and 0.5 ± 3.5 mmHg for SBP and DBP, respectively. CONCLUSION: The Senbiosys device is accurate enough to determine BP in a selected population undergoing coronary angiography.

Left atrial appendage closure with the II generation Ultraseal device: An international registry. The LIGATE study.

OBJECTIVES: To assess feasibility and safety of second-generation left atrial appendage closure (LAAC) Ultraseal device in patients with nonvalvular atrial fibrillation (NVAF). BACKGROUND: LAAC with first-generation Ultraseal device (Cardia, Eagan, Minnesota) has been shown to be a feasible therapeutic option in patients with NVAF. However, there is a paucity of data regarding the novel second-generation Ultraseal device. METHODS: All patients with NVAF undergoing second-generation Ultraseal device implantation between February 2018 and September 2020 were included in a multicenter international registry. Periprocedural and post-discharge events were collected through 6-month follow-up. Co-primary efficacy endpoints were device success and technical success while primary safety endpoint was in-hospital major adverse event (MAE) occurrence. RESULTS: A total of 52 patients were included: mean age 75 ± 8, 30.8% women, mean HAS-BLED 3 ± 1. The device was successfully implanted in all patients. Technical success was achieved in 50 patients (96.1%). In-hospital MAEs occurred in three patients (5.8%). The incidence of 6-month all-cause death and major bleeding was 11.6% and 2.1%, respectively. No strokes, transient ischemic attacks, systemic embolisms, or device embolization were reported after discharge. CONCLUSIONS: Second-generation Ultraseal device implantation was associated with high success rates and a low incidence of peri-procedural complications. Larger studies with longer follow-up are warranted to further evaluate the safety and the efficacy of this device, especially at long-term follow-up.

Cathepsin B-Cleavable Polymeric Photosensitizer Prodrug for Selective Photodynamic Therapy: In Vitro Studies.

Cathepsin B is a lysosomal cysteine protease that plays an important role in cancer, atherosclerosis, and other inflammatory diseases. The suppression of cathepsin B can inhibit tumor growth. The overexpression of cathepsin B can be used for the imaging and photodynamic therapy (PDT) of cancer. PDT targeting of cathepsin B may have a significant potential for selective destruction of cells with high cathepsin B activity. We synthesized a cathepsin B-cleavable polymeric photosensitizer prodrug (CTSB-PPP) that releases pheophorbide a (Pha), an efficient photosensitizer upon activation with cathepsin B. We determined the concentration dependant uptake in vitro, the safety, and subsequent PDT-induced toxicity of CTSB-PPP, and ROS production. CTSB-PPP was cleaved in bone marrow cells (BMCs), which express a high cathepsin B level. We showed that the intracellular fluorescence of Pha increased with increasing doses (3-48 µM) and exerted significant dark toxicity above 12 µM, as assessed by MTT assay. However, 6 µM showed no toxicity on cell viability and ex vivo vascular function. Time-dependent studies revealed that cellular accumulation of CTSB-PPP (6 µM) peaked at 60 min of treatment. PDT (light dose: 0-100 J/cm2, fluence rate: 100 mW/cm2) was applied after CTSB-PPP treatment (6 µM for 60 min) using a special frontal light diffuser coupled to a diode laser (671 nm). PDT resulted in a light dose-dependent reduction in the viability of BMCs and was associated with an increased intracellular ROS generation. Fluorescence and ROS generation was significantly reduced when the BMCs were pre-treated with E64-d, a cysteine protease inhibitor. In conclusion, we provide evidence that CTSB-PPP showed no dark toxicity at low concentrations. This probe could be utilized as a potential imaging agent to identify cells or tissues with cathepsin B activity. CTSB-PPP-based PDT results in effective cytotoxicity and thus, holds great promise as a therapeutic agent for achieving the selective destruction of cells with high cathepsin B activity.

Iodinated contrast media induced Kounis syndrome during coronary angiogram: a life-threatening clinical dilemma.

Kounis syndrome (KS) is a well-documented hypersensitivity vasospastic reaction induced by a variety of triggers. Clinical presentation ranges from non-specific symptoms such as dizziness and nausea to myocardial infarction. Many cases of KS were reported after the use of iodinated contrast media, mainly during radiological procedures. This report describes the case of a 46-year-old man developing coronary vasospasm and anaphylactic shock at the end of percutaneous coronary intervention. Occurrence of such pathology while performing coronary angiogram is a tricky situation for the invasive cardiologist. It requires recognising a rare syndrome and interrupting the procedure to avoid extra use of contrast media even in presence of severe coronary lesions due to vasospasm. Every interventionalist should be aware of such a presentation to recognise and react promptly when facing a potentially life-threatening clinical dilemma.