Optical Coherence Tomography in the Assessment and Management of Cardiac Allograft Vasculopathy.

PURPOSE OF REVIEW: Cardiac Allograft vasculopathy (CAV) is a major barrier to improving outcomes after heart transplantation. Coronary angiography has very low sensitivity to detect early CAV and intravascular ultrasound (IVUS) only improves it to some extent. In this article, we detail the current evidence surrounding use of Optical Coherence tomography (OCT) in patients with CAV. RECENT FINDINGS: OCT has the ability to recognize CAV at earlier stages with intimal thickness < 150 µm, can characterize CAV in almost pathologic / microscopic detail - plaque characteristics are better visualized and novel early features such as layered fibrotic plaques and microchannels have been identified. Progression of CAV can be monitored also, with promise shown in automated serial measurements also. OCT has significantly advanced our understanding of the pathophysiology-as well as permits precise monitoring and surveillance of the disease. Potential treatment options could also be evaluated using OCT.

Picosecond-resolved fluorescence resonance energy transfer (FRET) in diffuse reflectance spectroscopy explores biologically relevant hidden molecular contacts in a non-invasive way.

The potentiality of Förster resonance energy transfer (FRET) for studying molecular interactions inside biological tissues with improved spatial (Angström) and temporal (picosecond) resolution is well established. On the other hand, the efficacy of diffuse reflectance spectroscopy (DRS) that uses optical radiation in order to determine physiological parameters including haemoglobin, and oxygen saturation is well known. Here we have made an attempt to combine diffuse reflectance spectroscopy (DRS) with picosecond-resolved FRET in order to show improvement in the exploration of molecular contacts in biological tissue models. We define the technique as ultrafast time-resolved diffuse reflectance spectroscopy (UTRDRS). The illuminated photon of the fluorophore from the surface of the tissue-mimicking layers carries the hidden information of the molecular contact. In order to investigate the validation of the Kubelka-Munk (KM) formulism for the developed UTRDRS technique in tissue phantoms, we have studied the propagation of incandescent and picosecond-laser light through several layers of cellulose membranes. While picosecond-resolved FRET in the diffuse reflected light confirms the hidden nano-contact (4.6 nm) of two different dye layers (8-anilino-1-naphthalenesulfonic acid and Nile blue), high-resolution optical microscopy on the cross-section of the layers reveals the proximity and contacts of the layers with limited spatial resolution (∼300 nm). We have also investigated two biologically relevant molecules, namely carboxyfluorescein and haemoglobin, in tissue phantom layers in order to show the efficacy of the UTRDRS technique. Overall, our studies based on UTRDRS in tissue mimicking layers may have potential applications in non-invasive biomedical diagnosis for patients suffering from skin diseases.

Persistent or Recurrent Angina Following Percutaneous Coronary Revascularization.

PURPOSE OF REVIEW: Persistent or recurrent angina after percutaneous coronary intervention (PCI) has substantial patient morbidity and economic impact. As knowledge of the pathophysiology of this condition has evolved, new tools for accurate diagnosis and treatment have become available. We provide a current, comprehensive review of mechanisms of post-PCI angina, diagnostic strategies, and therapeutic options. RECENT FINDINGS: The routine use of functional testing during PCI may enable more accurate revascularization. Coronary vasomotor disorders commonly cause angina after PCI in the absence of obstructive epicardial CAD. Invasive coronary vasoreactivity testing can enable phenotype-guided therapy of coronary vasomotor disorders with improvement in angina. Multiple nonpharmacologic modalities to treat refractory angina are under development. A comprehensive approach to the diagnosis of persistent or recurrent angina after PCI with noninvasive and invasive techniques is required. An individualized, phenotype-guided management using lifestyle, pharmacologic, and nonpharmacologic modalities is necessary to optimize outcomes.

Congenital Pouch Colon with Segmental Dilatation of Ileum: Congenital Pouch Colon Type 6.

Congenital pouch colon (CPC) is classified on the basis of anatomic morphology into five types. Congenital segmental intestinal dilatation associated with anorectal malformation (ARM) is very rare. We are adding two neonates of CPC type 2 associated with segmental dilatation of the ileum to single similar case described in the literature till date. Temporary stomas with excision of either of the pouches should be considered. "Defective mesenchyme formation during organogenesis" due to abnormal mesenchymal precursor cells is hypothesized as the cause for both ARM and different types of CPC.

Intravascular ultrasound of normal left main arteries: Insights for stent optimization and standardization.

Left main (LM) lumen diameters >4 mm are the norm and diameter >4.5 mm is present in almost 50% of patients by intravascular ultrasound (IVUS). Normal LM minimum lumen area averages 14.1 mm2 for women and 16.2 mm2 for men, requiring an area stenosis of 57-63% for LM lesion to be hemodynamically significant using the prevailing criterion of 6 mm2 as a cut-off for revascularization. Incomplete LM visualization with IVUS is common (68%) without dedicated and specific LM IVUS techniques.

"Expanding the frame" for valve-in-valve therapy in small bioprostheses: Encouraging signs for the road ahead.

Valve in valve TAVI with valve fracture in 19 mm bioprosthetic valves is clinically effective. Careful multidisciplinary personalized evaluation for each patient is needed to prevent coronary occlusion. Longer term data for a larger number of patients are needed, from the transcatheter valve therapy (TVT) registry.

Embolic stroke of undetermined source and patent foramen ovale closure: Practice insights from meta-analysis?

Closure of patent foramen ovale (PFO) in embolic stroke of undetermined source (ESUS) reduces recurrent stroke compared with antiplatelet therapy in select patients but increases risk of atrial fibrillation. Device closure is an attractive option for young patients with an anatomically higher risk PFO and imaging proven ESUS. Benefit of PFO closure in ESUS compared with oral anticoagulation remains undefined.

Patent foramen ovale closure for cryptogenic stroke: Effective, but only in select patients.

PFO closure reduces risk of recurrent stroke in some patients with cryptogenic stroke, particularly younger patients <45 years with moderate or greater right to left shunting Number needed to treat (NNT) to prevent one stroke at 5 years are 28 to 69 (95% confidence limits of 21 to 351) suggesting need for individualized risk stratification models PFO closure may increase short- and possibly long-term risk of atrial flutter/fibrillation.

Patient preference: An important emerging factor in operator access site selection.

Patient preference should emerge as a third component influencing radial versus femoral access for cardiac catheterization. Ideally dually experienced "switch-operators" will consider co-morbidities, technical procedural factors, and patient preferences to choose a tailored approach with each patient. A tailored and tempered three component approach to access selection which includes patient preferences will likely optimize patient-centered outcomes.

The promise of effective P2Y12 platelet receptor pretreatment: Not crushed yet.

Pre-treatment with intact oral clopidogrel and prasugrel tablets in a representative observational study is not associated with altered ischemic or bleeding outcomes in acute coronary syndrome (ACS) patients. Limited by cost, cangrelor, a rapidly acting intravenous P2Y12 platelet receptor inhibitor, achieved meaningful reductions in major adverse cardiovascular events (MACE) and stent thrombosis (ST) compared to oral clopidogrel pretreatment. Crushed prasugrel and ticagrelor (CP&T) administered orally achieve accepted thresholds of therapeutic platelet inhibition in one hour in approximately 2/3rds of patients compared to 1/3rd with intact oral tablets. A large, simple randomized trial should test whether CP&T pre-treatment could capture some of the potential outcome benefit of rapid P2Y12 inhibition at no incremental risk and cost.

Ultrafast dynamics in co-sensitized photocatalysts under visible and NIR light irradiation.

Co-sensitization to achieve a broad absorption window is a widely accepted technique in light harvesting nanohybrid synthesis. Protoporphyrin (PPIX) and squaraine (SQ2) are two organic sensitizers absorbing in the visible and NIR wavelength regions of the solar spectrum, respectively. In the present study, we have sensitized zinc oxide (ZnO) nanoparticles using PPIX and SQ2 simultaneously for their potential use in broad-band solar light harvesting in photocatalysis. Förster resonance energy transfer (FRET) from PPIX to SQ2 in close proximity to the ZnO surface has been found to enhance visible light photocatalysis. In order to confirm the effect of intermolecular FRET in photocatalysis, the excited state lifetime of the energy donor dye PPIX has been modulated by inserting d10 (ZnII) and d7 (CoII) metal ions in the central position of the dye (PP(Zn) and PP(Co)). In the case of PP(Co)-SQ2, extensive photo-induced ligand to metal charge transfer counteracts the FRET efficiency while efficient FRET has been observed for the PP(Zn)-SQ2 pair. This observation has been justified by the comparison of the visible light photocatalysis of the respective nanohybrids with several control studies. We have also investigated the NIR photocatalysis of the co-sensitized nanohybrids which reveals that reduced aggregation of SQ2 due to co-sensitization of PPIX increases the NIR photocatalysis. However, core-metalation of PPIX reduces the NIR photocatalytic efficacy, most probably due to excited state charge transfer from SQ2 to the metal centre of PP(Co)/PP(Zn) through the conduction band of the host ZnO nanoparticles.

Length and pressure matter: Expediting evidence-based progress in femoropoliteal intervention.

Preprocedural lesion length and ankle-brachial indices (ABI) synergistically predict 12-month patency and repeat revacularization in claudicants treated with bare metal nitinol stents for femoropopliteal disease. This predictive length-ABI model will permit broader evidence-based indirect comparisons of newer femoropopliteal approaches such as drug eluting balloon treatment with or without atherectomy. The length-ABI model is a step to supplement and supplant randomized controlled trials with indirect comparisons as the necessary evidence source expediting innovation and optimizing personalized endovascular therapy for infrainguinal obstructive peripheral arterial disease.

Individualizing dual antiplatelet therapy duration: Prediction tools, genomics, and clinical judgment.

Prolonged dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) on average reduces the risk of subsequent myocardial infarction (MI) but increases major bleeds. Individualizing duration of DAPT based on the DAPT trial's net benefit prediction tool would likely optimize outcome beyond population average recommendations. Individualizing agent selection and duration of therapy based on genomic data may further improve outcomes. Clinical judgment remains the most important tool to tailor DAPT duration based on a large array of additional relevant factors not captured by predition rules or genomics.

Unprotected Left Main Disease and Percutaneous Intervention: A Prototype for Precision Medicine.

The SYNTAX Score based on angiographic findings is an actionable risk prediction model helping guide treatment for significant unprotected left main disease. Adding the clinical factor based EuroSCORE to SYNTAX improves outcome prediction for percutaneous coronary intervention of unprotected left main disease. Prediction models are an increasingly useful tool permitting cardiologists to optimize patient outcomes through "personalized" or precision medicine.

Trans-septal approach for percutaneous closure of infra-diaphragmatic veno-venous collateral in a patient after Fontan palliation.

In this article, we present a case of a desaturated Fontan patient with an infra-diaphragmatic venous collateral to the pulmonary vein, which was too tortuous to attempt closure at the source. A trans-septal approach was successfully used to close the collateral in a retrograde manner.

Trends and Disparities in Valvular Heart Disease Mortality in the United States From 1999 to 2020.

BACKGROUND: Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real-world mortality data on valvular heart disease (VHD) in the United States remain limited. METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age-adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22-year study, there were 446 096 VHD deaths, accounting for 0.80% of all-cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD-related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2-8.5) to 6.6 (95% CI, 6.5-6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR. CONCLUSIONS: The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.

Aortic Valve Replacement in Patients With ESRD and Heart Failure With Reduced Ejection Fraction.

Transcatheter aortic valve replacement (TAVR) has become the standard of care for the treatment of all patients with calcific aortic stenosis. Patients with end-stage renal disease (ESRD) on hemodialysis were excluded from participation in many of the seminal trials proving the safety and efficacy of TAVR. The outcomes of TAVR in the ESRD population from a national registry showed significantly higher in-hospital and 1-year mortality compared with patients not on hemodialysis. Comparisons of outcomes for surgical versus transcatheter interventions in patients with ESRD and heart failure with reduced ejection fraction (HFrEF) are limited. Using the United States Renal Data System, we identified all ESRD patients with aortic stenosis and HFrEF who underwent TAVR, surgical aortic valve replacement (SAVR), or those with HFrEF and aortic stenosis initiated on dialysis after the year 2012 to compare survival. Propensity score matching was performed, and groups were compared using Kaplan-Meier curves. The study population consisted of 7,660 patients, of which 5,064 (66.1%) were male. The median age at initiation of dialysis was 73 years (interquartile range: 65 to 80). There were 1,108 (14.5%) who underwent TAVR and 695 (9.1%) who underwent SAVR. After matching, patients who underwent TAVR had increased survival relative to those who were medically managed. In-hospital outcomes favored TAVR with less mortality and fewer complications when compared with SAVR. TAVR had improved mortality relative to SAVR in the early period, but survival curves crossed at approximately 9 months and SAVR had better mortality in the long-term. TAVR is a safe and effective procedure and is associated with improved mortality when compared with medical management. In conclusion, TAVR and SAVR are both viable options for patients with ESRD and HF with TAVR having better short-term outcomes and SAVR better long-term outcomes.

Randomized trial of an oblique versus standard fluoroscopic-guided micropuncture technique for femoral arterial access: The Micropuncture-CFA trial.

BACKGROUND: The anterior-posterior fluoroscopic guidance (the AP technique) is a standard method for common femoral artery (CFA) access, but the rate of CFA access with ultrasound vs. the AP technique was not significantly different. We have shown an oblique fluoroscopic guidance (the oblique technique) with a micropuncture needle (MPN) resulted in CFA access in 100 % of patients. The outcome of the oblique vs. AP technique is unknown. We compared the utilities of the oblique vs. AP technique for CFA access with a MPN in patients undergoing coronary procedures. METHODS: A total of 200 patients were randomized to the oblique vs. AP technique. Using the oblique technique, a MPN was advanced to the mid pubis in the 20° ipsilateral right-or left anterior oblique view with fluoroscopic guidance and the CFA was punctured. In the AP technique, a MPN was advanced to the mid femoral head in the AP view with fluoroscopic guidance and the CFA was punctured. The primary endpoint was the rate of successful access to the CFA. RESULTS: The rates of first pass and CFA access were higher with the oblique vs. AP technique (82 % vs. 61 %, and 94 % vs. 81 %, respectively; P < 0.01). The number of needle punctures was lower with the oblique vs. AP technique (1.1 ± 0.39 vs. 1.4 ± 0.78, respectively; P < 0.01). In high CFA bifurcations, the rate of CFA access was higher with the oblique vs. AP technique (76 % vs. 52 %, respectively; P < 0.01). Vascular complications were lower with the oblique vs. AP technique (1 % vs. 7 %, respectively; P < 0.05). CONCLUSIONS: Our data suggest that the oblique technique, compared with the AP technique, significantly increased the rates of first pass and access to the CFA, and decreased the number of punctures and vascular complication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03955653.

Aortic valve disorders and left ventricular assist devices.

Aortic valve disorders are important considerations in advanced heart failure patients being evaluated for left ventricular assist devices (LVAD) and those on LVAD support. Aortic insufficiency (AI) can be present prior to LVAD implantation or develop de novo during LVAD support. It is usually a progressive disorder and can lead to impaired LVAD effectiveness and heart failure symptoms. Severe AI is associated with worsening hemodynamics, increased hospitalizations, and decreased survival in LVAD patients. Diagnosis is made with echocardiographic, device assessment, and/or catheterization studies. Standard echocardiographic criteria for AI are insufficient for accurate diagnosis of AI severity. Management of pre-existing AI includes aortic repair or replacement at the time of LVAD implant. Management of de novo AI on LVAD support is challenging with increased risks of repeat surgical intervention, and percutaneous techniques including transcatheter aortic valve replacement are assuming greater importance. In this manuscript, we provide a comprehensive approach to contemporary diagnosis and management of aortic valve disorders in the setting of LVAD therapy.