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.

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.

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.

Percutaneous Large Thrombus and Vegetation Evacuation in the Catheterization Laboratory.

Intracardiac and intravascular thrombi are associated with significant morbidity and mortality. Although surgery remains the gold standard treatment option, these patients often have multiple comorbidities that can make surgical options challenging. With advancements in catheter-based technologies, there are now percutaneous treatment options for these patients. The AngioVac is a percutaneous vacuum-assisted thrombectomy device FDA-approved for removal of intravascular debris that uses a venovenous extracorporeal membranous oxygenation circuit with a filter. Use of this device has now been reported in the removal of right atrial or iliocaval thrombi, debulking tricuspid vegetations, removal of vegetations from implantable cardiac devices, and pulmonary embolism.

Racial and rural-urban disparities in cardiovascular risk factors among patients with head and neck cancer in a clinical cohort.

BACKGROUND: Evidence on distribution of cardiovascular disease (CVD) risk factors in patients with head and neck squamous cell carcinoma (HNSCC) is limited. We assessed disparities in prevalence and incidence of CVD risk factors in patients with HNSCC. METHODS: Electronic health records (EHR) data on 2262 patients with HNSCC diagnosed between 2012 and 2018 at a NCI-designated cancer center were included. Prevalence of CVD risk factors at baseline and incidence at 1-year post HNSCC diagnosis were assessed using logistic and robust Poisson regression, respectively. RESULTS: At baseline, 31.72% white patients with HNSCC had dyslipidemia, compared to 24.29% blacks (p < 0.008); diabetes was more prevalent in blacks (p < 0.027). Odds of ≥1 prevalent CVD clinical risk factor at baseline was lower in blacks (OR, 95%CI: 0.71, 0.54-0.93) and in rural patients (OR, 95%CI: 0.70, 0.58-0.85). At 1 year, risk of incident diabetes was higher in rural patients (RR, 95%CI: 1.63, 1.21-2.19). CONCLUSIONS: Demographic disparities were observed in distribution of CVD risk factors in patients with HNSCC.

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.

Dual Sensitization via Electron and Energy Harvesting in a Nanohybrid for Improvement of Therapeutic Efficacy.

We demonstrate experimental evidence of the effect of surface plasmon resonance of noble metal nanoparticles (NPs) on the activity of a well-known biomedicinal drug in the proximity of a semiconductor having a wide band gap for enhanced photodynamic therapy (PDT) efficacy. We have chosen riboflavin (Rf) (or vitamin B2) as a model photosensitizer, attached with ZnO NPs and further attached with gold (Au) NP-decorated ZnO to increase the efficiency. The synthesized nanohybrids are characterized with the help of different microscopic, optical spectroscopic, and density functional theory (DFT)-based techniques. The DFT and time-dependent DFT-based calculations validate the experimental findings. A detailed ultrafast spectroscopic study has been carried out further to study the excited-state charge dynamics in the interface of the nanohybrids. The occurrence of a Förster resonance energy transfer (FRET) between Rf and Au has been found to be the key reason for the increased efficiency in the Rf-ZnO-Au nanohybrid over the Rf-ZnO one. The dipolar coupling between Au and Rf in the Rf-ZnO-Au nanohybrid further facilitates the generation of reactive oxygen species (ROS) in comparison to Rf-ZnO under blue-light irradiation. The greater efficiency in ROS generation by the Rf-ZnO-Au nanohybrid has been utilized for antimicrobial action against methicillin-resistant S. aureus (MRSA). Overall, the present study highlights the dual sensitization for achieving enhanced electron injection efficiency in the Rf-ZnO-Au nanohybrid in order to use it as an antibacterial agent that could be translated in PDT.

Traditional risk factors and cancer-related factors associated with cardiovascular disease risk in head and neck cancer patients.

Background: Risk of incident cardiovascular disease (CVD) in head and neck squamous cell carcinoma (HNSCC) patients is under-reported. We assessed the association of HNSCC-related factors and traditional risk factors with 1- and 5-year CVD risk in HNSCC patients without prevalent CVD at cancer diagnosis. Methods: A clinical cohort of 1,829 HNSCC patients diagnosed between 2012 and 2018, at a National Cancer Institute (NCI)-designated cancer center was included. Information on HNSCC-related factors [HNSCC anatomical subsite, stage at diagnosis, treatment, and tumor human papillomavirus (HPV) status] were extracted from the tumor registry. Data on traditional risk factors (hypertension, dyslipidemia, diabetes, tobacco smoking status, and obesity) were extracted from the electronic health records system (EHR) at baseline (HNSCC diagnosis). A composite of ischemic heart disease, heart failure, and ischemic stroke was the outcome of interest in time to event analysis. Hazard ratio (HR) (95% CI) were reported with death as a competing risk. Results: In patients diagnosed with HNSCC, 10.61% developed incident CVD events by 1-year post cancer diagnosis. One-year CVD risk was lower in patients using antihypertensive medications at baseline, compared to patients without baseline hypertension [HR (95% CI): 0.41 (0.24-0.61)]. One-year CVD risk was high in patients receiving HNSCC surgery. Patients receiving radiation therapy had a higher 5-year CVD risk than surgery patients [HR (95% CI): 2.17 (1.31-3.04)]. Patients using antihypertensive medications had a lower 5-year CVD risk than patients without baseline hypertension [HR (95% CI): 0.45 (0.22-0.75)]. Older age and diabetes were associated with increased 1- and 5-year CVD risk. HPV-negative patients were older (p 0.006) and had a higher 5-year cumulative incidence of CVD (p 0.013) than HPV-positive patients. Conclusion: Traditional risk factors and cancer-related factors are associated with CVD risk in HNSCC patients. Future research should investigate the role of antihypertensive medications in reducing CVD risk in HNSCC patients.

Five-meter walk test before transcatheter aortic valve replacement and 1-year noncardiac mortality.

Objective: The purpose of this study is to assess whether the 5-m walk test is associated with 1-year mortality after transcatheter aortic valve replacement. Methods: Included in the analysis were 304 patients who received the 5-m walk test and underwent transcatheter aortic valve replacement from September 2012 to March 2019. They were classified into 3 groups based on their test score: ≤7, >7, and unable to walk. Preprocedure characteristics, postprocedure outcomes, and follow-up outcomes were compared between the groups. Results: For the 5-m walk test, 145 had a score ≤7 (Group N), 111 had a score >7 (Group S), and 48 were unable to walk (Group I). Average age in years was 80.2 ± 8.7 years in Group N, 81.2 ± 9.4 years in Group S, and 79.4 ± 9.2 in Group I (P = .23). The aortic valve mean gradient at discharge was 9.5 ± 4.1 mm Hg in Group N, 10.4 ± 5.5 mm Hg in Group S, and 8.2 ± 4.2 mm Hg in Group I (P = .05). The discharge survival was 97.2% in Group N, 96.4% in Group S, and 95.8% in Group I (P = .76). One-year survival was 92.8% in Group N, 84.1% in Group S, and 75% in Group I (P < .01) after adjusting for preprocedure characteristics. Noncardiac death was 5.1% in Group N, 13.1% in Group S, and 22.7% in Group I (P = .03). This indicates that the 5-m walk test was a risk factor for 1-year mortality. More specifically, a poor 5-m walk test score was associated with 1-year noncardiac mortality. Conclusions: The 5-m walk test score before transcatheter aortic valve replacement was associated with 1-year mortality, especially noncardiac mortality. It may help identify patients at high risk for 1-year mortality.

Optical Coherence Tomography in Cardiac Allograft Vasculopathy: State-of-the-Art Review.

Cardiac allograft vasculopathy (CAV) is a challenging complication of heart transplantation. CAV pathophysiology is incompletely understood, standard screening modalities such as angiography have significant limitations, and currently available therapies have only modest efficacy in preventing progression. Optical coherence tomography is a light-based technique that provides microscopic level catheter-based intravascular imaging and has dramatically expanded our understanding of CAV, demonstrating it to be a complex, heterogeneous, and dynamic process. This review covers characteristics and uses of optical coherence tomography, including vessel characterization, serial use to assess progression of disease, guiding percutaneous intervention, and monitoring response to CAV therapies. We also discuss the potential of optical coherence tomography in providing individualized assessment and enable customized CAV therapies, which may lead to improvements in long-term transplant outcomes.

Transcatheter pulmonic valve implantation: Techniques, current roles, and future implications.

Right ventricular outflow tract (RVOT) obstruction is present in a variety of congenital heart disease states including tetralogy of Fallot, pulmonary atresia/stenosis and other conotruncal abnormalities etc. After surgical repair, these patients develop RVOT residual abnormalities of pulmonic stenosis and/or insufficiency of their native outflow tract or right ventricle to pulmonary artery conduit. There are also sequelae of other surgeries like the Ross operation for aortic valve disease that lead to right ventricle to pulmonary artery conduit dysfunction. Surgical pulmonic valve replacement (SPVR) has been the mainstay for these patients and is considered standard of care. Transcatheter pulmonic valve implantation (TPVI) was first reported in 2000 and has made strides as a comparable alternative to SPVR, being approved in the United States in 2010. We provide a comprehensive review in this space-indications for TPVI, detailed procedural facets and up-to-date review of the literature regarding outcomes of TPVI. TPVI has been shown to have favorable medium-term outcomes free of re-interventions especially after the adoption of the practice of pre-stenting the RVOT. Procedural mortality and complications are uncommon. With more experience, recognition of risk of dreaded outcomes like coronary compression has improved. Also, conduit rupture is increasingly being managed with transcatheter tools. Questions over endocarditis risk still prevail in the TPVI population. Head-to-head comparisons to SPVR are still limited but available data suggests equivalence. We also discuss newer valve technologies that have limited data currently and may have more applicability for treatment of native dysfunctional RVOT substrates.

Pulmonary Vascular Disease Due to Plasma Cell Dyscrasia.

Pulmonary hypertension (PH) has been described in myeloproliferative disorders; monoclonal plasma cell disorder such as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome; and plasma cell dyscrasias such as multiple myeloma and amyloidosis. We describe 4 cases of PH likely due to pulmonary vascular involvement and myocardial deposition from light chain deposition disease, amyloidosis, and multiple myeloma. On the basis of our clinical experience and literature review, we propose screening for plasma cell dyscrasia in patients with heart failure with preserved ejection fraction, unexplained PH, and hematological abnormalities. We also recommend inclusion of cardiopulmonary screening in patients with monoclonal gammopathy of undetermined significance.