Citations

Background: Heavily calcified coronary bifurcation lesions present significant challenges during percutaneous coronary intervention, particularly during atherectomy due to the risk of side branch occlusion from plaque shift. We describe the "Double Guiding Catheter Technique" to minimize side branch closure and wire damage to non-atherectomy vessels during bifurcation orbital atherectomy (OA). Case: A 74-year-old male with a recent NSTEMI presented for elective coronary artery revascularization. A coronary angiogram revealed non-obstructive left coronary arteries and a dominant right coronary artery (RCA) with heavily calcified stenosis at the bifurcation of the right posterolateral (RPL) and right posterior descending (RPD) branches. After placing temporary transvenous pacing and inserting sheaths in the right radial and right femoral arteries, both the RPL and RPD were wired with coronary guidewires. Using a coronary microcatheter, the wire in RPL was replaced with a ViperWire guidewire for OA, while the microcatheter in RPD served as guidewire protection. OA of RPL was successfully performed with the Diamondback 360° OA system (Cardiovascular Systems Inc), followed by multiple dilatations with non-compliant balloons and placement of two drug-eluting stents in the distal RCA to RPL and RPD, achieving good angiographic and IVUS results. Discussion: The Double Guiding Catheter Technique has been described in a few case reports of heavily calcified left main coronary bifurcation atherectomy which is limited to relatively proximal lesions due to the need to pass a second wire to a non-atherectomy vessel outside a guide extension catheter for the main branch. This is the first reported case of OA using this technique in the right coronary artery and a relatively distal part of the coronary artery. The primary advantage of this technique is eliminating the need to withdraw one of the two wires, which can be challenging when recrossing the side branch. The microcatheter can safely protect the other branch wire during atherectomy. Conclusion: By maintaining both wires with a protective microcatheter, OA of coronary bifurcation stenosis can be successfully achieved, potentially reducing the risk of wire transection.

Background: AI-ECG is a cost-effective tool for left ventricular dysfunction (LVD) screening. However, its cost-effectiveness for other forms of structural heart disease (SHD) is unknown. While AI-ECG is inexpensive, a drawback is low positive predictive value (PPV), which leads to high costs from unnecessary follow-up tests. Therefore, strategies to improve the yield of AI-ECG-based screening are needed. Aim: To evaluate the cost savings of a stepwise approach to SHD screening with AI-ECG followed by POCUS compared to AI-ECG alone. Methods: 286 adult outpatients undergoing AI-ECG were selected at random. Participants received same-day POCUS and had a recent TTE (our gold standard for SHD). We evaluated four SHDs: aortic stenosis (AS), cardiac amyloidosis (CA), HCM, and LVD. The costs of AI-ECG ($75) and TTE ($1,305) were obtained from Healthcare Bluebook. The cost of POCUS ($100) was estimated independently. Cost savings were analyzed for simultaneous screening for all forms of SHD and screening for individual SHDs. Results: AI-ECG identified potential SHD in 125 patients, but only 39 were true positives by TTE (31% PPV). In AI-ECG positive patients, POCUS demonstrated findings of SHD in 52/125. Compared to TTE, this stepwise approach yielded 32 true positives and 20 false positives (62% PPV). The cost per patient diagnosed with SHD was $4,733 with AI-ECG alone but decreased to $3,182 with stepwise screening (33% cost savings). Screening for individual SHDs resulted in cost reduction from $18,724 to $6,315 (66% savings) for AS, $21,023 to $12,230 (42% savings) for CA, $9,883 to $6,175 (38% savings) for HCM, and $4,019 to $3,582 (11% savings) for LVD. Conclusions: Stepwise screening for SHD with AI-ECG followed by POCUS significantly reduces costs compared to AI-ECG alone. We also suggest a model for parallel screening for multiple SHDs, which is likely more cost-effective than screening for individual SHDs.

Background: Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing after diagnosing atrial fibrillation (AF). Purpose: We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on AF recurrence, all-cause mortality, stroke, and heart failure (HF) after AF catheter ablation. Methods: We comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through February 2024. We conducted a pair-wise and prognostic systematic review and meta-analysis with a reconstructed time-to-event data meta-analysis. All analyses were performed using R V. 4.3.1. PROSPERO ID: CRD42024525542. Results: With the inclusion of 22 studies, our cohort comprised a total of 42,101 patients. Regarding pair-wise meta-analysis, shorter DAT was significantly associated with a decreased incidence of AF recurrence across paroxysmal and persistent AF subgroups. Moreover, DAT ≤ one year was significantly associated with a decreased incidence of all-cause mortality (RR: 0.73 with 95% CI [0.59, 0.92], P< 0.01) with a trend toward lowering the risk of stroke (RR: 0.80 with 95% CI [0.62, 1.03], P= 0.08). However, there was no significant difference between DAT ≤ one year and DAT > one year in HF. Regarding adjusted prognostic meta-analysis, longer DAT was significantly associated with an increased risk of AF recurrence (P < 0.01). Our reconstructed Kaplan Meier showed that DAT > one year was significantly associated with a 50% increase in the risk of AF recurrence compared to DAT ≤ one year (HR: 1.50 with 95% CI [1.42, 1.58], P< 0.00001) over 60 months follow-up. Conclusion: Our meta-analysis strongly underscores the critical importance of a short DAT in significantly reducing AF recurrence and all-cause mortality, with a trend toward lowering stroke risk, though no significant impact on HF was observed. Early ablation proves beneficial not only for patients with paroxysmal AF but also for those with persistent AF. These findings suggest that minimizing DAT can markedly improve AF outcomes, warranting further investigation to optimize treatment strategies.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal condition characterized by worsening heart failure (HF), exercise intolerance, cardiac arrhythmias, aortic stenosis, and orthopedic manifestations. Recent analyses have shown ATTR-CM presents a significant burden to the healthcare system, but data on healthcare resource utilization (HCRU) comparing ATTR-CM to non-ATTR HF in the US are lacking. Aim: To compare HCRU and costs in patients (pts) with ATTR-CM to that of pts with non-ATTR HF using medical and pharmacy claims. Methods: Using the Optum Clinformatics Data Mart (Jan 2016-Sep 2023), pts with ATTR-CM were identified based on presence of HF and/or cardiomyopathy (CM) occurring within 2 years of first amyloidosis diagnosis (excluding light-chain amyloidosis) and followed for at least 12 months after first HF/CM diagnosis. ATTR-CM pts were matched 1:1 to non-ATTR HF pts using propensity score matching. After index diagnosis, both groups were assessed for HCRU, including inpatient acute cardiovascular (CV) hospitalizations (CVH), length of stay, and cost. Hospitalizations were considered CV if a pt received a CV diagnosis during the hospitalization period. Results: There were 4581 pts with ATTR-CM (mean [±SD] age: 76 [9.13] years; 56.2% male) who met inclusion criteria and were matched to 4581 non-ATTR HF pts (mean [±SD] age: 76 [8.86] years; 56.0% male) for comparison (Table). ATTR-CM pts had a higher trend of CVH and a higher number of total CVHs and mean hospitalizations per pt compared to non-ATTR HF pts (p<0.001). The mean cost per hospitalization (p=0.00463) and mean cost per annual hospitalizations per pt (p<0.001) were higher for ATTR-CM compared to non-ATTR HF. ATTR-CM pts were also hospitalized for more mean days annually for CV-related reasons compared to non-ATTR HF pts (p<0.001). On average, pts with ATTR-CM spent 2.3 days more than matched non-ATTR HF pts in the hospital each year. Conclusion: Compared to non-ATTR HF, ATTR-CM is associated with a greater burden on the healthcare system as evaluated by hospitalization rate, costs per hospitalization, annual hospitalization costs, and days hospitalized annually.

Background: Myocarditis is a dreaded complication of immune-checkpoint inhibitor (ICI) therapy but challenging to diagnose. There are no published data comparing the two leading diagnostic criteria for ICI myocarditis and their association with cardiovascular events. Methods: Patients treated with ICI and cardiac Troponin (cTnT) measurements thereafter at a tertiary institution from 2011 to 2022 were identified. Charts were reviewed for ICI-related myocarditis according to the Bonaca et. al criteria and the ESC-ICOS guideline criteria. A propensity matched control group was identified of patients treated with ICI but without developing myocarditis. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death, MACE (myocardial infarction, TIA/stroke, new heart failure diagnosis), and arrhythmias (V-tach, A-fib, complete heart block). Results: A total of 59 patients were identified as having a diagnosis of ICI-related myocarditis per Bonaca criteria (16 having definite, 13 probable and 30 possible myocarditis), and 47 met the ESC-ICOS guideline criteria. Mean age was 73.1±10.2 years, 60.1% were male, median follow-up was 2.5 years. ICI-related myocarditis as diagnosed by both diagnostic criteria had prognostic value for cardiac death (HR 13.94, 95%CI 1.84-105.64, p=0.011 per Bonaca, HR 6.22, 95%CI 1.77-21.88, p=0.004 per ESC-ICOS), MACE, (HR 3.17, 95%CI 1.34-7.47, p=0.008 per Bonaca, HR 2.97, 95%CI 1.37-6.45, p=0.006 per ESC-ICOS), and arrhythmias (HR 1.93, 95%CI 1.10-3.38, p=0.022 per Bonaca, HR 2.09, 95%CI 1.21-3.60, p<0.001 per ESC-ICOS), (Figures 1 and 2). There was no significant difference for cardiac death (AUC 0.75 for Bonaca, AUC 0.74 for ESC, p=0.765) or MACE (AUC 0.66 for Bonaca, AUC 0.66 for ESC, p=0.916) when both criteria were compared with each other. Conclusion: The ESC-ICOS criteria were more restrictive than the Bonaca criteria for the diagnosis of ICI-related myocarditis but similar in terms of prognostic value.

Background: Catheter ablation (CA) is an effective treatment for atrial fibrillation (AF), but many patients experience recurrence post-intervention. Evaluating left atrial strain (LAS) to measure LA reservoir strain (LASr), conduit strain (LAScd), and contractile strain (LASct) could help predict AF recurrence, especially in patients with no evident signs of severe LA myopathy. Goal: This study aims to assess the prognostic value of pre-ablation LAS in both paroxysmal AF (paAF) and persistent AF(peAF) in patients with no evident signs of severe LA myopathy. Methods: This retrospective study encompassed AF patients who underwent their first CA procedure at Mayo Clinic Arizona from October 2018 to February 2022 and had a LAVI <40 ml/m2 and LVEF >55%. Transthoracic echocardiography parameters, including the three LAS phases, were collected using TOMTEC software on the closest date before the CA procedure. Receiver operating characteristic (ROC) curve analysis was used to evaluate the capability of LAS to detect patients with AF recurrence after CA from those without recurrence. Results: Out of 335 AF patients who underwent CA during the study period, 40 cases had LAVI <40 ml/m2 and LVEF >55% (72.5% male; mean age 69.2 ± 8 years). Of these, 15% (6/40) experienced recurrence, while 85% (34/40) maintained sinus rhythm. The mean values of LASr, LAScd, and LASct for all patients were 16.82, 11.23, and 6.87, respectively. ROC analysis indicated that the area under the curve (AUC) for LASr, LAScd, and LASct was 0.582, 0.502, and 0.710, respectively. (Graph 1A, Table 1A) LASct was the only parameter associated with AF recurrence (AUC: 0.71). Additionally, we developed a novel marker termed LAVI-LASct by combining LAVI and LASct values, which demonstrated improved discrimination with an ROC value of 0.74 (Graph 1B). Conclusions: LASct demonstrated predictive capability for AF recurrence in patients with no severe LA dilation and preserved LVEF, potentially due to its ability to detect early atrial dysfunction preceding visible structural changes or myocardial pathology. The addition of LAVI values provided better discrimination for the ROC model. Further research is needed to confirm the clinical relevance of LAS in AF patients undergoing ablation.

Introduction: Intracranial aneurysms are associated with local degradation of the vessel wall resulting in the formation of a blood-filled sac. Approximately 6 million people are estimated to have intercranial saccular aneurysms in the US alone. Most aneurysms remain undetected until rupture, resulting in hemorrhage which carries a high mortality rate (>50%). Flow diverters are placed across the aneurysm neck to divert blood flow away from the sac, preventing rupture once occluded. However, flow diverters carry significant risk for thromboembolism, which is a major cause of morbidity. The elevated risk of thromboembolism is likely due to endothelial injury of the parent artery at the neck of the aneurysm. We hypothesize that the bionanomatrix can promote faster endothelialization and aneurysm occlusion thereby reducing the risk of thromboembolism after flow diverter treatment. Methods: The bionanomatrix is composed of peptide amphiphiles containing endothelial cell adhesive ligand (YIGSR) and a nitric oxide (NO) donor (KKKKK), both components critical for recruiting and retaining endothelial cells on the device. The NO releasing bionanomatrix was coated onto the flow diverters using ultrasonic spray coating, and the NO effects on endothelial cell (EC) and smooth muscle cell (SMC) proliferation on the coated devices was assessed, in vitro, using calcien-AM staining. For the in vivo study, an elastase-induced rabbit aneurysm model was created. The bionanomatrix coated and uncoated flow diverters were implanted into the rabbit aneurysm model for 4 weeks. The coated and uncoated flow diverters were then analyzed for endothelialization, smooth muscle cell proliferation, and aneurysm occlusion by angiography, gross image, and immunohistochemistry analyses. Results: In vitro , the bionanomatrix coated flow diverters significantly enhanced endothelial cell proliferation as well as reduced smooth muscle cell proliferation on the flow diverters compared to the uncoated device. In vivo, after 4 weeks, the bionanomatrix coated flow diverters demonstrated enhanced neck coverage, more complete endothelialization, and reduced smooth muscle thickness on the coated flow diverters compared to the uncoated devices as seen by gross image analysis and histology. Conclusions: The bionanomatrix coated flow diverters can successfully promote faster endothelialization and brain aneurysm occlusion which is critical for reducing the risk of thromboembolism after neurointervention.

Background: The optimal timing of pacemaker reimplantation following transvenous lead removal (TLR) of infected cardiac implantable electronic device (CIED) remains unclear. Objective: Our study aimed to assess the impact of timing to pacemaker reimplantation after TLR of infected CIED on hospital outcomes. Method: Using the Nationwide Readmissions Database, patients aged ≥18 years who underwent new pacemaker implantation with percutaneous approach following TLR of infected CIED from 2017 to 2020 were identified. The study population was stratified based on the timing of pacemaker reimplantation following TLR of infected CIED: early (<5 days) vs delayed (≥5 days). Weighted-propensity-score matched conditional multivariable logistic regressions were performed to determine the impact of the timing on various outcomes. Results: In our study, 469 (66.9%) patients received early device reimplantation, and 232 (33.1%) patients received delayed device reimplantation (≥5 days). Post-procedurally, patients in the delayed group had a higher risk of prolonged hospital stay (95% CI OR: 42.37 (6.36 – 282.11); p<0.01) and non-home discharge (95% CI OR: 2.00 (1.35 – 2.95), p<0.01). There was no significant difference between both groups in the early mortality, 30-day readmission, and procedural complications. Conclusion: Our study suggests that time-to-device reimplantation from TLR of infected CIED did not affect the overall short-term in-hospital outcomes. However, delayed device reimplantation was associated with a higher rate of prolonged hospital stay and non-home discharge.

Introduction: An elevated blood pressure (mean arterial pressure, MAP) response to exercise is an independent predictor of hypertension (HTN) development. HTN is highly prevalent in postmenopausal females. Postmenopausal, compared to premenopausal, females have a higher MAP at rest and during exercise primarily due to higher systemic vascular resistance (SVR). Studies using small muscle mass exercise have suggested that postmenopausal females have augmented increases in MAP from rest to exercise. However, it is unclear if postmenopausal females have augmented MAP responses from rest to exercise during whole-body exercise. Hypothesis: We hypothesized that postmenopausal females would have greater increases in MAP and smaller decreases in SVR from rest to peak exercise than premenopausal females. Methods: Normotensive premenopausal (n=16; age: 30±7 yrs; BMI: 23±4 kg/m 2 ) and postmenopausal (n=14; age: 57±7 yrs; BMI: 27±4 kg/m 2 ) female participants performed an incremental cycling test until task failure. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) via open-circuit acetylene wash-in technique, and SVR was calculated. Data are reported at rest and peak oxygen uptake (VO 2 ). Data are also reported as % change from rest to VO 2 peak. Results: Postmenopausal females had higher MAP and SVR at rest and at VO 2 peak than premenopausal females (all, p<0.05). Postmenopausal, compared to premenopausal, females had lower Q at VO 2 peak commensurate with the lower achieved VO 2 peak (p<0.01). Resting MAP was positively related to MAP at VO 2 peak in postmenopausal females (r=0.85, p<0.01), but not premenopausal females (p=0.22). % change in MAP from rest to VO 2 peak was not different between groups (Post: 18±8 vs. Pre: 18±9%) (p=0.94). However, postmenopausal females had smaller % decreases in SVR from rest to VO 2 peak (Post: -44±7 vs. Pre: -54±8%) and smaller % increases in Q compared to premenopausal females (Post: 113±31 vs. Pre: 162±50%) (both, p<0.01). Conclusion: Our findings indicate that postmenopausal and premenopausal females have similar increases in MAP from rest to VO 2 peak; however, the mechanisms contributing to the MAP response differed by menopausal status. Postmenopausal females relied on smaller decreases in SVR, whereas premenopausal females had greater increases in Q. These findings provide important insight into the mechanisms contributing to the clinically relevant higher MAP response during exercise in postmenopausal females.

Background: Tyrosine kinase inhibitors (TKIs), such as sunitinib, are highly effective in treating cancers. However, they have severe cardiovascular (CV) side effects that include cardiotoxicity via cardiomyocyte injury and death resulting in myocardial dysfunction. There are no FDA-approved drugs to prevent or treat cardiotoxicity, which have been linked mechanistically to mitochondrial dysfunction and oxidative stress, highlighting the need for new therapeutics. Two recognized CV protective pathways are the particulate guanylyl cyclase A receptor (GC-A)/cGMP and the Mas receptor (MasR)/cAMP pathways. We recently engineered NPA7 a novel peptide that activates both pathways. Aim: Here we investigated NPA7’s ability to protect against sunitinib-induced cardiotoxicity in human cardiomyocytes (HCMs) and defined its role on mitochondrial function. Methods: HCMs were treated with DMSO or sunitinib (10 µM) together with PBS or NPA7 (10 µM). Intracellular reactive oxygen species (ROS) was assessed by DHE staining. CCK8 assay was performed to measure cell viability. TOM20 staining were performed by immunofluorescence and the mitochondrial length was analyzed. The protein levels of mitochondrial dynamics markers (fission: MFF, Fis1; fusion: OPA1 and MFN1) proteins were measured by western blot. Cell surface area was assessed by phalloidin staining with mRNA levels of hypertrophic gene markers (NPPA and MYH7) in HCMs using real-time PCR. Results: Sunitinib increased DHE staining and intracellular ROS in HCMs, which was decreased with NPA7 treatment. NPA7 enhanced HCM cell viability in the presence of sunitinib. TOM20 staining showed a marked reduction in mitochondrial length in sunitinib group, compared to DMSO group, whereas NPA7 treatment rescued mitochondria length (DMSO= 6.15 ± 0.94 μm, Sunitinib= 2.42 ± 0.63 μm, NPA7= 5.4 ± 1.19 μm; P < 0.05). Moreover, NPA7 inhibited mitochondrial fission protein levels (MFF and Fis1) and increased mitochondrial fusion protein levels (OPA1, MFN1) in HCMs treated with sunitinib. Sunitinib treatment notably increased HCM cell surface area and hypertrophic gene markers (NPPA and MYH7), whereas NPA7 abolished these markers of hypertrophy. Conclusions: We report, for the first time, that NPA7 protects against sunitinib induced oxidative stress, mitochondrial fragmentation, hypertrophy and cell death in HCMs. These data support a novel therapeutic approach against TKI-induced cardiotoxicity with NPA7 to which no therapies exist.