Citations

Background: The outcomes of leadless pacemaker (LP) implantation after transvenous lead removal (TLR) of infected cardiac implantable electronic devices (CIED) are not well-established. Objective: This study sought to describe the outcomes of LP implantation following TLR of infected CIED. Method: We conducted a literature search using PubMed and Embase for a combination of term including leadless pacemaker implantation, transvenous lead extraction, transvenous lead removal , transvenous lead explant , infected cardiac implantable electronic device . The inclusion criterion was LP implantation after TLR of infected CIED. The exclusion criterion was TLR for non-infectious reason. Study end-points were procedural complications and LP infection. Result: Of 132 publications reviewed, 13 studies with a total of 253 patients (74 ± 14 years of age, 69% males) were included. Amongst, 56.8% had systemic CIED infection and 43.2% had isolated pocket infection. Staphylococcus Aureus was the most common causative organism in 33% of the reported patients. Of 253 patients included, 105 patients (41.5%) underwent concomitant LP implantation during TLR procedure, and 36 patients (14.2%) had transvenous pacing as a bridge from TLR to LP implantation. During the LP implantation, 1 patient (0.4%) had an intra-procedural complication requiring sternotomy. Post-LP implantation, 2 patients (0.8%) developed groin hematoma, 2 patients (0.8%) developed femoral arteriovenous fistula, and 1 patient (0.4%) developed pericardial effusion requiring pericardiocentesis. During a mean follow-up of 11.3 ±10.6 months, 3 patients (1.2%) developed pacemaker syndrome, 1 patient (0.4%) developed acute on chronic heart failure exacerbation, and only 1 patient (0.4%) developed LP-related infection requiring LP retrieval. Conclusion: This study suggests that LP implant is feasible and safe post-removal of infected CIED with cumulative adverse events at 4% and a reinfection rate of 0.4%.

Case description: A 67 year old female presented for annual review to the transplant clinic 4 years post orthotopic heart transplant for nonischemic dilated cardiomyopathy. She was asymptomatic. Her medical history included hypothyroidism, hypertension, osteoporosis, restless leg syndrome and calcineurin inhibitor related complications - CKD 3b, impaired glucose tolerance and a left partial glossectomy with neck dissection for stage 3 SCC of the left lateral tongue. Medications included aspirin, atorvastatin, prednisolone, tacrolimus, septrin and ropinirole. Family history was significant for heart failure in her father. She was a nonsmoker and did not consume alcohol. Physical examination was unremarkable. Diagnostic tests are shown below. Discussion: Apical hypertrophic cardiomyopathy (ApHCM) has rarely been described in post cardiac transplant populations. Characterized by increased left ventricular apical wall thickness, it results in a ‘spade-like’ appearance on imaging and is associated with marked T wave inversion on ECG. ApHCM is associated with progression to heart failure, apical aneurysm, ventricular arrhythmias and increased mortality rates. Patients may be asymptomatic at diagnosis. Regarding screening, criteria exist for the selection of donor hearts pre transplant with caution exercised if LVH >13mm. Causes of non HCM hypertrophy in this population include calcineurin inhibitors, hypertension, obesity and graft versus host disease. Data for treatment for ApHCM is lacking however it follows the path of classical HCM, involving the use of beta and calcium channel blockers to reduce demand ischemia and management of sequelae.

Introduction: Patients with coronary artery disease (CAD) are at increased risk of cognitive decline. A proposed mechanism is cerebral hypoperfusion related to vascular dysfunction and impaired cerebral blood flow regulation Hypothesis: Patients with CAD will have lower cerebrovascular function than age- and sex-matched controls, assessed as reactivity to a vasodilatory carbon dioxide (CO 2 ) stimulus. Methods: Adults 40-70years old with CAD were recruited on enrollment to a cardiac rehabilitation program following a cardiac event or hospitalization. Age and sex-matched adults without known disease or cardiovascular risk factors were recruited as healthy controls. Cognitive function was assessed by the Fluid Composite of the NIH Cognition Toolbox. Following a familiarization visit, participants underwent a stepped CO 2 protocol (room air, 2% CO 2 , 4% CO 2 , 6% CO 2 ) while continuously measuring middle cerebral artery velocity (MCAv) using transcranial doppler ultrasound, mean arterial pressure (MAP), ventilation (VE), and end-tidal CO 2 . Cerebrovascular conductance (CVCi) was calculated as MCAv/MAP. Cerebrovascular reactivity was calculated as the linear regression slope of CVCi against the change in end-tidal CO 2 . The reactivity of MAP and VE (or chemosensitivity) were also calculated. Results: 19 patients with CAD and 10 healthy controls were recruited ( Table 1 ). Compared with controls, patients with CAD had a 2-fold lower cerebrovascular reactivity (p=0.003), higher MAP reactivity (p<0.05), and a trend towards higher chemosensitivity (p<0.1) ( Table 2 ). There were no group differences in resting CVCi or cognition ( Table 2 ). After adjustment for age and sex, lower cerebrovascular reactivity was associated with lower peak oxygen uptake, diabetes, and smoking history ( Table 3 ). Conclusions: Compared with healthy controls, we report that patients with CAD have significantly lower cerebrovascular function, with no differences in cognitive function.

Background: Fabry's disease (FD), an X-linked lysosomal storage disorder, can present with cardiac manifestations similar to HCM. We aim to emphasize considering FD as a differential diagnosis in patients with HCM while highlighting the role of genetic testing in evaluating left ventricular hypertrophy (LVH). Cases Presentation: We present a case series of 3 patients with LVH. Despite initial clinical suspicion of primary HCM, genetic testing confirmed the diagnosis of FD. Patient 1: A 38-year-old male with no prior medical history presented with presyncope, lightheadedness, and chest tightness. EKG, Echo, and cardiac MRI suggested apical HCM. Genetic testing indicated FD. Patient 2: A 62-year-old male sought a second opinion regarding his diffuse HCM. EKG suggested RBBB. Echo showed a binary appearance of the myocardium, concentric LVH. Genetic testing confirmed FD. Patient 3: A 64-year-old male with a history of hypertension and renal disease underwent evaluation for kidney transplantation. Echo showed severely increased concentric LVH and Valsalva-induced intracavitary gradient/obstruction. Alpha-galactosidase level returned very low, suggesting FD, which was confirmed by genetic testing. Discussion: FD can be challenging to diagnose due to overlapping clinical and imaging features with HCM, leading to misdiagnosis and delayed management. Therefore, Genetic testing should be offered to all patients with suspected HCM to exclude phenocopies. Particularly, those with progressive HCM and atypical clinical features (renal disease and family history predominantly in males) and imaging features (conduction abnormalities on EKG, binary appearance on Echo). Early identification of FD enables appropriate management, including enzyme replacement therapy, potentially improving clinical outcomes. Conclusions: FD should be considered as a differential diagnosis in patients with HCM. Genetic testing plays a vital role in evaluating patients with HCM.

Introduction: The ICD Sports Registry demonstrated that many athletes with ICDs can participate in competitive sports without death, failure to defibrillate, or physical injury. However, sudden cardiac arrest is more prevalent and has worse outcomes in Black compared to White individuals in the general population and among athletes. Outcomes of sports participation for Black athletes with ICDs have not been described. Aim: To describe the risk of arrhythmia and efficacy of ICDs in Black athletes. Methods: This is a post-hoc subgroup analysis of the ICD Sports Registry, which enrolled athletes with ICDs age 10 to 60, participating in organized, competitive sports, and followed them prospectively for four years. The endpoints and methods are reported previously. Results: Among the 440 athletes, 15 were Black and 410 white. Among the Black athletes, hypertrophic cardiomyopathy was the most common diagnosis (40%) and 87% were implanted for secondary prevention or syncope (vs 69% in White athletes). Most common sports were basketball (8), softball (4), and running (3), with 7 Black athletes competing on varsity/junior varsity/traveling teams. Among the Black athletes, there were no appropriate shocks during sports, among white athletes, 7% received an appropriate shock during sports. Among Black athletes, there was one appropriate shock event for ventricular tachycardia (7%), a VT storm in an athlete with idiopathic VF, non-sports-related. Among white athletes, 10% received appropriate shocks during non-sports activities. Two Black athletes (13%) received an inappropriate shock, one competition-related (sinus tachycardia) and the other for T wave oversensing at rest, vs 12% of white athletes. There were no sports-related deaths, arrests, or arrhythmia-related injuries in either group. Conclusions: Black athletes represented a small subset of the ICD Sports Registry. Reasons for this are unknown, but may include disparities in ICD implantation and/or in research recruitment/ participation. These Black athletes experienced both appropriate and inappropriate shocks as did white athletes. These data do not suggest a signal for harm for competitive sports participation for Black athletes with ICDs but larger studies are needed.

Introduction: Cardiac amyloidosis (CA) has been suggested to be common (up to 16%) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). CA has poorer outcomes and its assessment in all TAVR patients may be costly and challenging. Hypothesis: CA may be screened for with an artificial intelligence (AI) clinical predictive model applied to pre-TAVR ECGs, and high probability (>50%) for CA may be associated with worse clinical outcomes. Methods: In this retrospective analysis of the Mayo institutional National Cardiovascular Disease Registry (NCDR)-TAVR, patients undergoing a TAVR between Jan-2012 and Dec-2017 were included. Pre-TAVR ECGs were analyzed by the AI predictive model for CA embedded in the EMR. EMRs were reviewed to assess for a clinical diagnosis of CA in those identified as high probability (>50%) by the AI tool. Clinical outcomes on 1 year follow-up were extracted from the NCDR-TAVR database and Kaplan-Meier curves were created to compare patients with high CA probability (≥50%) versus those with low probability (<50%). Results: Of 1070 patients who underwent TAVR (mean age 81.1± 8.5 years, 58.2% male), 263 (24.6%) had ≥50% probability for CA on pre-procedure ECG. Only 18 (1.7%) of these had clinical diagnosis of CA. In the survival analysis, high probability of CA by AI tool was associated with higher all-cause mortality (HR 1.60, 95%CI 1.09-2.34, p=0.01) and greater HF admissions (HR 1.59, 95%CI 1.08-2.35, p<0.01). Neither TIA/stroke nor myocardial infarction were statistically significant. MACE (TIA/stroke, myocardial infarction, heart failure admissions) was higher in the ≥50% CA probability group (HR 1.68, 95%CI 1.17-2.40, p<0.01), (Figure) . Conclusion: CA is clinically underdiagnosed in patients undergoing TAVR. AI applied to pre-TAVR ECGs suggesting higher probability for CA identifies a subgroup at higher risk of clinical events, who may benefit from further diagnostic evaluation for CA.

Introduction: Left ventricular diastolic function and filling pressure (FP) can be assessed by echocardiography and cardiac catheterization. Recently, a novel artificial intelligence (AI)-enabled ECG has proven to be effective in identifying increased FP determined by echocardiographic assessment of diastolic function. Aims: We aimed to compare a prognostic value of AI-ECG determination of FP compared to echocardiography and catheterization. Methods: This study included 4,213 patients who had a transthoracic echocardiogram and ECG within 30 days before hemodynamic cardiac catheterization. Increased FP was defined as pulmonary artery wedge pressure >15 mmHg by catheterization and grade 2 or 3 diastolic dysfunction by echocardiography based on diastolic function guidelines. Increased FP by ECG was identified using previously developed AI-ECG. AI-ECG performance was evaluated using the area under the curve (AUC) of the receiver operating curve. We assessed the risk of all-cause mortality using Kaplan-Meier estimate and multivariable Cox proportional-hazards models. Results: AI-ECG had AUCs of 0.8 and 0.7 for predicting increased FP determined by echocardiography and catheterization, respectively. Death was observed in 2,776 (34%) patients over a median follow-up of 7.7 years (IQR 7.1, 8.3). Survival of patients with normal and increased FP by AI-ECG, Echocardiography, and catheterization are shown in Figure 1a. Concordant diagnoses of normal and increased FP by AI-ECG and catheterization or echocardiography had the highest and lowest survival rates, respectively. When FP by AI-ECG was discordant, survival was better predicted by AI-ECG compared to echocardiography and catheterization (Figure 1b). Conclusion: AI-ECG for FP has a potential to discriminate prognosis further compared to FP determined by echocardiography or catheterization.

Introduction: Excess cardiomyocyte oxidative stress is a major metabolic abnormality in HTN and its progression to HF. Thus, therapies that reduce oxidative stress in the heart may lead to a reduction in CVD related adverse outcomes such as HF and death. Recently, we bioengineered a bispecific peptide NPA7 that co-activates the protective GC-A/cGMP and MasR/cAMP pathways. Previously we showed that NPA7 possesses cardiorenal protective properties. However, the antioxidant effects of NPA7 within the heart is unknown. Hypothesis: NPA7 protects human cardiomyocytes against oxidative stress through the GC-A/Mas Receptor-KEAP1-NRF2 pathway. Methods: HCMs were pretreated with PBS or NPA7 (10 uM) followed by 400 uM hydrogen peroxide (H2O2) to induce oxidative stress. Intracellular ROS was measured by dihydroethidium (DHE) staining and protein levels of KEAP1 and NRF2 via western blot. The ratio of GSH/GSSG were determined by using commercial kit. mRNA levels of G6PD, GCLC, GCLM and GSS in HCMs, which represents antioxidant capacity, were determined by real-time PCR. For knockdown experiments, HCMs were transfected with the siRNA target GC-A and MasR for 24 h and then treated with NPA7 and H2O2 for another 20 h. Results: H2O2 increased DHE staining level, which indicated elevated intracellular ROS levels within HCMs. Notably, treatment with NPA7 decreased DHE level and increased the ratio of GSH/GSSG in HCMs with H2O2. Furthermore, NPA7 significantly increased the mRNA level of NRF2 target genes (G6PD, GCLC, GCLM, GSS) through NRF2 activation and KEAP1 degradation, indicating that NPA7 activates KEAP1-NRF2 pathway, the upstream pathway that regulate antioxidant gene expression, in HCMs. Moreover, these effects were eliminated if GC-A and MasR were silenced by siRNA, thus supporting the protective antioxidant role of both GC-A and MasR. Conclusions: The present study establishes an antioxidant action of NPA7, a novel bispecific designer peptide, on H2O2-induced oxidative stress by the dual targeting of GC-A and MasR through the KEAP1-NRF2 signaling pathway in HCMs. These results advance NPA7 as an innovative therapeutic strategy targeting oxidative stress related to CVD.

Introduction: The right ventricle [RV] adapts to pulmonary hypertension [PH] by increasing contractility to maintain RV-PA coupling. With increased afterload, RV contractility cannot compensate, resulting in RV failure. TAPSE/RVSP ratio is a non-invasive measure of RV-PA coupling. We aim to assess TAPSE/RVSP ratio for predicting PH severity and survival across a spectrum of PH in the PVDOMICS cohort. Methods: PVDOMICS subjects from the 5 World Symposium PH groups and comparators were evaluated. TAPSE/RVSP ratio, in mm/mmHg, was derived for each group. PH subjects were stratified by TAPSE/RVSP ratio into low < 0.19, intermediate ≥ 0.19 to < 0.32, and high ratio > 0.32. The relationship between the ratio and RHC parameters (mean PA pressure [mPAP] and pulmonary vascular resistance [PVR]), and between-group differences were evaluated by one-way ANOVA. Kaplan-Meier curves and log-rank tests were used to characterize and compare survival between groups. Results: Data were available for 514 PH subjects (58 ± 15 yrs, 64% female) and 179 comparators (61 ± 13 yrs, 59% female). Mean TAPSE/RVSP ratio was 0.35 ± 0.18 in PH vs 0.63 ± 0.26 in comparators (p < 0.001). Mean TAPSE/RVSP across the PH groups 1-5 were similar, 0.33 ± 0.19, 0.33 ± 0.16, 0.37 ± 0.15, 0.41 ± 0.21 and 0.43 ± 0.29 (p=NS). Within PH subjects, 99 (19.2%) had low, 173 (33.7%) had intermediate and 242 (47.1%) had high ratio. Those with low ratio had higher mPAP (53.6 ± 11.8 mmHg), compared to intermediate (44.6 ± 11.7 mmHg) and high ratio (34.1 ± 10.2 mmHg) [p < 0.001]. Those with low ratio had higher PVR (10.1 ± 5.1 WU), compared to intermediate (6.8 ± 4.1 WU) and high ratio (4.1 ± 2.1 WU) [p < 0.001]. Survival was significantly higher for those with high TAPSE/RVSP ratio compared to those with low ratio (p < 0.001) [Figure]. Discussion: TAPSE/RVSP ratio correlates well with invasive markers to predict PH severity. This useful measure of RV-PA coupling also enables stratification for outcome, with ratio > 0.32 having the best survival rates.

Introduction: Pulmonary vein thrombosis (PVT) is often diagnosed incidentally but data on its management and outcomes are sparse. Methods: We queried our institutional health record to identify patients ≥18 years of age diagnosed with PVT. Demographics, medications, risk factors, diagnostics, treatment, and sequelae were collected by manual chart review. Suspected tumor thrombus cases were excluded. Results: Seventy-two patients with PVT were identified (median age 62 years, 50% male). The cohort was mostly white (85%), overweight (BMI 26 kg/m), with frequent comorbidities including hypertension (44%), hyperlipidemia (38%), atrial fibrillation/flutter (29%), and history of venous thromboembolism (21%). The most common PVT risk factors were active malignancy (54%), lobectomy (21%), surgery within 30 days (19%), and extrinsic vein compression (15%). Most PVT were diagnosed by CT (86%) and affected a single vein (86%), mostly commonly the left upper PV (32%). Laboratory studies revealed median platelet count 243 х 10 9 cells/L (n=58) and D-dimer elevated in 6 patients when measured (67%, n=9). About one-third of patients were on therapeutic anticoagulation (37%) at PVT diagnosis. Most patients were started on new anticoagulation (78%, n=56), with unfractionated heparin as the most common initial therapy (68%). Of those anticoagulated, few were treated with a limited duration (20%, n=11, median 54 d, IQR 95) while most received indefinite anticoagulation (80%, n=45), primarily warfarin (45%), apixaban (24%), or enoxaparin (21%). Serial imaging was obtained in 69% (n=50, median 65 d, IQR 116) and demonstrated resolution of PVT in 32 (64%) patients. Common PVT complications noted were as follows: 4 year risk of LA thrombus (26%, 12/16 anticoagulated), mechanical ventilation (13%), pneumonia (9%), and ischemic stroke (9%, 5/6 anticoagulated). Conclusions: PVT is often associated with active malignancy, lobectomy, recent surgery, and extrinsic vein compression. Most PVT resolve on serial imaging. Clinicians should be aware of potential high-risk sequelae including LA thrombus and stroke as well as high anticoagulation failure rates when managing PVT.