Leadless pacemaker with transcatheter aortic valve implantation: A single-center experience.

BACKGROUND: The safety and efficacy of leadless pacemakers (LP) in transcatheter aortic valve implant (TAVI) patients is not well known due to paucity of data. Herein, we compared outcomes between leadless pacemakers to traditional dual chamber pacemakers (DCP) following TAVI. METHODS: A single-center retrospective study was conducted, including a total of 27 patients with LP and 33 patients with DCP after TAVI between November 2013 and May 2021. We compared baseline demographics, pacemaker indications, complication rates, percent pacing, and ejection fractions. RESULTS: Leading indications for pacemaker implant were complete heart block (74% LP, 73% DCP) and high degree atrioventricular block (26% LP, 21% DCP). Twenty-two (82%) LP patients had devices implanted in the right ventricular septal-apex. Three (9%) DCP patients required rehospitalization for pocket related complications. Zero pacemaker-related mortality was observed in both groups. Frequency of ventricular pacing and ejection fraction was similar between LP and DCP groups. CONCLUSION: From this single-center retrospective study, LP implant was feasible following TAVI and was found to have comparable performance to DCPs. LPs may be a reasonable alternative in TAVI patients where single ventricular pacing is indicated. Larger studies are required to validate these findings.

A Special Clinical Scenario for Transcatheter Aortic Valve Replacement: "Iatrogenic Double-Outlet" Left Ventricle.

A 67-year-old man with a history of chest radiotherapy and severe aortic valve stenosis with calcification of the ascending aortic wall underwent implantation of an apicoaortic conduit from the left ventricular apex to the descending aorta. Eight years later, he presented with progressive exertional dyspnea. Imaging revealed severe native aortic valve insufficiency and calcification, with worsening left ventricular function. We decided to leave the apicoaortic conduit intact and perform transcatheter aortic valve replacement with a balloon-expandable prosthesis. Despite concerns that eliminating the obstruction across the native left ventricular outflow tract might decrease conduit flow and eventually cause graft thrombosis and peripheral embolization, we elected to move forward after a multidisciplinary discussion. The procedure resulted in angiographically and qualitatively similar forward flow across the newly implanted prosthesis and the existing apicoaortic conduit, with no hemodynamic or electrical dysfunction. The patient was discharged from the hospital the next day. At the 1-month follow-up visit, the patient felt well and reported marked functional improvement, with minimal symptoms during moderate to heavy exertion. The stroke volume index across the new bioprosthetic valve was low (13 mL/m2 at 1 mo and 18 mL/m2 at 1 y), suggesting that a substantial amount of blood was still exiting the ventricle through the left ventricle-to-aorta conduit. This report offers some guidance for treating patients with existing apicoaortic conduits and suggests that transcatheter aortic valve replacement is safe and effective if native aortic valve insufficiency develops.

Hemodynamic outcomes after valve-in-valve transcatheter aortic valve replacement: a single-center experience.

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as a safe, effective alternative to redo aortic valve surgery in high-risk patients with degenerated surgical bioprosthetic valves. However, ViV-TAVR has been associated high postprocedural valvular gradients, compared with TAVR for native-valve aortic stenosis. METHODS: We performed a retrospective study of all patients who underwent ViV-TAVR for a degenerated aortic valve bioprosthesis between January 1, 2013 and March 31, 2019 at our center. The primary outcome was postprocedural mean aortic valve gradient. Outcomes were compared across surgical valve type (stented versus stentless), surgical valve internal diameter (≤19 versus >19 mm), and transcatheter aortic valve type (self-expanding vs. balloon-expandable). RESULTS: Overall, 89 patients underwent ViV-TAVR. Mean age was 69.0±12.6 years, 61% were male, and median Society of Thoracic Surgeons Predicted Risk of Mortality score was 5.4 [interquartile range, 3.2-8.5]. Bioprosthesis mode of failure was stenotic (58% of patients), regurgitant (24%), or mixed (18%). The surgical valve was stented in 75% of patients and stentless in 25%. The surgical valve's internal diameter was ≤19 mm in 45% of cases. A balloon-expandable transcatheter valve was used in 53% of procedures. Baseline aortic valve area and mean gradients were 0.87±0.31 cm2 and 36±18 mmHg, respectively. These improved after ViV-TAVR to 1.38±0.55 cm2 and 18±11 mmHg at a median outpatient follow-up of 331 [67-394] days. Higher postprocedural mean gradients were associated with surgical valves having an internal diameter ≤19 mm (24±13 versus 16±8, P=0.002) and with stented surgical valves (22±11 versus 12±6, P<0.001). CONCLUSIONS: ViV-TAVR is an effective option for treating degenerated surgical aortic bioprostheses, with acceptable hemodynamic outcomes. Small surgical valves and stented surgical valves are associated with higher postprocedural gradients.

Association of acute kidney injury with outcomes in patients undergoing percutaneous left atrial appendage closure.

OBJECTIVES: Using a large nationally representative database, we aimed to examine risk factors for acute kidney injury (AKI) and its association with outcomes in patients undergoing percutaneous left atrial appendage closure (LAAC). BACKGROUND: Previous small-scale studies have reported poor outcomes with AKI following percutaneous LAAC. METHODS: We queried the Nationwide Readmission Database to identify LAAC procedures performed from 2016 to 2017. Multivariable logistic and linear regression models were used to identify risk factors for AKI and determine the association between AKI and clinical outcomes. The primary outcome of interest was in-hospital mortality. RESULTS: Of 20,703 patients who underwent LAAC during the study period, 1,097 (5.3%) had a diagnosis of AKI. Chronic kidney disease, non-elective admission, coagulopathy, weight loss, prior coronary artery disease, heart failure, diabetes mellitus, and anemia were independently associated with an increased risk of AKI after LACC. In patients undergoing LAAC, AKI was associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR], 16.01; 95% CI, 8.48-30.21), stroke/transient ischemic attack (aOR, 2.50; 95% CI, 1.69-3.70), systemic embolization (aOR, 3.78; 95% CI, 1.64-8.70), bleeding/transfusion (aOR, 1.96; 95% CI, 1.50-2.56), vascular complications (aOR, 3.53; 95% CI, 1.94-6.42), pericardial tamponade requiring intervention (aOR, 6.83; 95% CI, 4.37-10.66), index length of stay (adjusted parameter estimate, 7.46; 95% CI, 7.02-7.92), and 180-day all-cause readmissions (aOR, 1.43; 95% CI, 1.09-1.88). CONCLUSION: AKI in the setting of LAAC is uncommon but is associated with poor clinical outcomes. Further studies are needed to determine if a similar association exists for long-term outcomes.

Transcatheter aortic valve replacement after chest radiation: A propensity-matched analysis.

BACKGROUND: Chest radiation therapy (CRT) for malignant thoracic neoplasms is associated with development of valvular heart disease years later. As previous radiation exposure can complicate surgical treatment, transcatheter aortic valve replacement (TAVR) has emerged as an alternative. However, outcomes data are lacking for TAVR patients with a history of CRT. METHODS: We conducted a retrospective study of all patients who underwent a TAVR procedure at a single institution between September 2012 and November 2018. Among 1341 total patients, 50 had previous CRT. These were propensity-matched in a 1:2 ratio to 100 patients without history of CRT. Thirty-day adverse events were analyzed with generalized estimating equation models. Overall mortality was analyzed with stratified Cox regression modelling. RESULTS: Median clinical follow-up was 24 months (interquartile range [IQR], 12-44 months). There was no difference between CRT and non-CRT patients in overall mortality (hazard ratio [HR] 0.84 [0.37-1.90], P = 0.67), 30-day mortality (HR 3.1 [0.49-20.03], P = 0.23), or 30-day readmission rate (HR 1.0 [0.43-2.31], P = 1). There were no differences in the rates of most adverse events, but patients with CRT history had higher rates of postprocedural respiratory failure (HR 3.63 [1.32-10.02], P = 0.01) and permanent pacemaker implantation (HR 2.84 [1.15-7.01], P = 0.02). CONCLUSIONS: For patients with aortic valve stenosis and previous CRT, TAVR is safe and effective, with outcomes similar to those in the general aortic stenosis population. Patients with history of CRT are more likely to have postprocedural respiratory failure and to require permanent pacemaker implantation.

Targeting Inflammation After Myocardial Infarction.

PURPOSE OF REVIEW: Inflammation plays a key role in clearing cellular debris and recovery after acute myocardial infarction (AMI). Dysregulation of or prolonged inflammation may result in adverse cardiac remodeling and major adverse clinical events (MACE). Several pre-clinical studies and moderate sized clinical trials have investigated the role of immunomodulation in improving clinical outcomes in patients with AMI. RECENT FINDINGS: Clinical data from the Canakinumab Atherothrombosis Outcome (CANTOS) and Colchicine Cardiovascular Outcomes Trial (COLCOT) have provided encouraging results among patients with AMI. Several other clinical and pre-clinical trials have brought about the prospect of modulating inflammation at various junctures of the inflammatory cascade including inhibition of complement cascade, interleukins, and matrix metalloproteinases. In patients with AMI, modulation of residual inflammation via various inflammatory pathways and mediators may hold promise for further reducing MACE. Learning from current data and understanding the nuances of immunomodulation in AMI are key for future trials and before widespread dissemination of such therapies.

Role of preoperative cardiac CT in the evaluation of infective endocarditis: comparison with transesophageal echocardiography and surgical findings.

BACKGROUND: Significant improvement of computed tomography (CT) technology in the last decade has led to more use of this modality for evaluating infective endocarditis (IE) especially since the introduction of high resolution electrocardiogram (ECG) synchronized multiphasic (4D) acquisition. While there are a number of reports on the accuracy and value of 4D CT for evaluation of IE, there is no published data regarding the performance of single-phase ECG gated CT for assessment of IE. The purpose of this study is to evaluate the sensitivity and specificity of preoperative single-phase ECG-gated CT imaging versus transesophageal echocardiography (TEE) in the assessment of complications related to IE, with comparison to surgical findings. METHODS: Among 899 patients with surgically proven IE in our database, 122 underwent contrast-enhanced ECG cardiac CT and were included in the study; 84 of these patients also underwent TEE. RESULTS: Overall, there was no significant difference between CT and TEE in the identification of pseudoaneurysm/abscess and dehiscence. For the detection of pseudoaneurysm/abscess in prosthetic valves, CT demonstrated higher sensitivity (81% vs. 64%) and specificity (75% vs. 33%) in patients with mechanical aortic valves; TEE demonstrated marginally higher sensitivity (72% vs. 63%) and specificity (80% vs. 73%) in patients with bioprosthetic aortic valves, although the differences are not statistically significant. TEE demonstrated significantly higher sensitivity (85% vs. 16%) in identifying vegetation in all patients (P<0.0001), including patients with prosthetic valves (sensitivity, 78% vs. 19%). The combined imaging findings of CT and TEE demonstrated improved sensitivity in identifying pseudoaneurysm/abscess and slightly improved detection of prosthesis dehiscence. CONCLUSIONS: Preoperative single-phase gated CT can be seen as complementary to TEE in assessing complications of suspected IE or may be substituted for TEE when vegetation or dehiscence is depicted on transthoracic echocardiography and the patient has a contraindication to TEE.

Risk stratification with exercise N(13)-ammonia PET in adults with anomalous right coronary arteries.

OBJECTIVE: In adults with an interarterial and intramural course of an anomalous right coronary artery from the left sinus (AAORCA), surgical unroofing is recommended in the setting of myocardial ischaemia. However, data regarding functional testing are limited, and the management of adults without ischaemia is unclear. To evaluate these patients, we employed an exercise N(13)-ammonia positron emission tomography (PET) protocol. We hypothesised that patients with typical angina and exertional dyspnoea would be more likely to have ischaemia and that patients without ischaemia could be managed conservatively. METHODS: Between July 2008 and December 2014, we retrospectively identified 27 consecutive patients >18 years old with an interarterial and intramural course of an AAORCA who had exercise N(13)-ammonia PET. RESULTS: The majority of patients had anatomic delineation with cardiac CT (25, 93%), and most patients had chest pain (24, 89%). Myocardial ischaemia with PET was common (13, 48%), and ischaemia was more likely in patients with typical angina and exertional dyspnoea (p<0.05). Surgery was performed in 12 patients including 11 patients with ischaemia. At a median follow-up of 245 days, there were no deaths in patients with surgery or in patients managed conservatively. CONCLUSIONS: In patients with an interarterial and intramural course of an AAORCA, typical angina and exertional dyspnoea are associated with ischaemia on exercise N(13)-ammonia PET. Referral for surgical unroofing in symptomatic patients with ischaemia on exercise N(13)-ammonia PET and initial conservative management in patients without ischaemia seems appropriate, though larger studies with long-term follow-up are needed.

Temporal Variability of Global Longitudinal Strain in Stable Patients Undergoing Chemotherapy With Trastuzumab.

Global longitudinal strain (GLS) is used to evaluate left ventricular (LV) performance after chemotherapy. Differentiating between reduction in GLS due to clinical change and normal temporal variability in measurement remains a challenge. We quantified interobserver, test-retest variability of GLS by expert observers in relation to variability of GLS quantified for clinical assessment by sonographers in our laboratory. We examined the temporal variability of GLS in 30 patients with normal LV ejection fraction (LVEF >53%) undergoing chemotherapy in the absence of change in medications and clinical symptoms in up to 5 sequential echocardiograms. GLS was quantified using EchoPAC (GE Healthcare, Milwaukee, Wisconsin) and 2-dimensional biplane LVEF was measured from 4- and 2- chamber views. Interobserver test-retest variability of GLS measured in 10 random patients by 2 expert readers was calculated using a one-way analysis of variance. Square root of mean squared error provided the SEM for temporal variability. Baseline LVEF was 59.3 ± 5.1% and remained relatively unchanged over 12 months, p = 0.87. Temporal variability of GLS measured by sonographers was 1.28% and similar to interobserver test-retest variability of GLS measured by expert observers, 1.12% (p = 0.17). Maximum detectable difference in GLS measured by expert observers was similar to that derived from sequential measurements of GLS (3.2% vs 3.6%, respectively). Temporal variability of GLS among clinically stable patients is 1.28% and similar to interobserver test-retest variability of 1.12% measured by expert observers. In conclusion, a reduction in strain >3.2% during sequential echocardiograms under these conditions may be significant.

Association of left ventricular strain with 30-day mortality and readmission in patients with heart failure.

BACKGROUND: Heart failure (HF) readmissions are a common and serious problem of heterogeneous etiology. Left ventricular (LV) ejection fraction has not been found to be a consistent risk marker. However, LV strain has been shown to predict outcomes in other settings, so the aim of this study was to determine the association of LV strain with 30-day HF readmission, independent of and incremental to clinical and basic echocardiographic parameters. METHODS: A total of 468 patients who underwent echocardiography at the time of the first admission for HF from July 2009 to June 2012 were retrospectively studied. Clinical parameters were comprehensively assessed, and standard echocardiographic parameters and two strain parameters (global longitudinal strain [GLS] and global circumferential strain) were measured using speckle-tracking. Patients were followed for all-cause 30-day hospital readmission or death after discharge, and the associations of parameters with outcome were assessed using Cox proportional hazards models. RESULTS: Readmission within 30 days (n = 92 patients [20%]) was associated with greater impairment of LV GLS (-8.6% [interquartile range, -10.9% to -5.9%] vs -11.1% [interquartile range, -14.6% to -7.7%], P < .01). The association of GLS with readmission (hazard ratio, 1.13; 95% confidence interval, 1.07-1.19; P < .01) was independent of age, male gender, systolic blood pressure, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and comorbidity, as well as renal function, sodium, hematocrit, LV mass, left atrial size, and mitral regurgitation. Global circumferential strain was associated with outcome but not was independent after adjustment with echocardiographic parameters. In sequential models for 30-day outcome, GLS added incremental information to clinical parameters and LV ejection fraction and significantly improved reclassification (categorical net reclassification improvement, 0.34; P = .04) when LV ejection fraction was >50%. CONCLUSIONS: GLS is associated with HF readmission, independent of and incremental to clinical and basic echocardiographic parameters.

Hypereosinophilic syndrome associated with ulcerative colitis presenting with recurrent Loeffler's endocarditis and left ventricular thrombus treated successfully with immune suppressive therapy and anticoagulation.

We reported a case of a 28-year-old Caucasian woman with hypereosinophilic syndrome (HES) associated with ulcerative colitis who presented on separate occasions with Loeffler's endocarditis. She was admitted in 2008 with fever, headache, confusion and visual loss. Diagnostic workup uncovered an eosinophilia of 3.1×109/L and major ECG abnormalities. Subsequent echocardiography revealed left ventricular wall motion abnormalities with mural thrombus. MRI brain scan showed multiple white matter lesions consistent with acute infarcts. She recovered rapidly with corticosteroids and anticoagulation. Four years later she re-presented with headache, fatigue and an eosinophilia of 13.4×109/L. This occurred 3 months after cessation of immunosuppression and within 12 months of total colectomy for fulminant ulcerative colitis. Echocardiography was suggestive of hypereosinophilic endomyocardial fibrosis with left ventricular thrombus. Anticoagulation and corticosteroids were resumed with good effect. This report highlights the findings, treatment and outcome of ulcerative colitis-associated HES manifesting as recurrent Loeffler's endocarditis.

Thioredoxin-1 gene therapy enhances angiogenic signaling and reduces ventricular remodeling in infarcted myocardium of diabetic rats.

BACKGROUND: The present study evaluated the reversal of diabetes-mediated impairment of angiogenesis in a myocardial infarction model of type 1 diabetic rats by intramyocardial administration of an adenoviral vector encoding thioredoxin-1 (Ad.Trx1). Various studies have linked diabetes-mediated impairment of angiogenesis to dysfunctional antioxidant systems in which thioredoxin-1 plays a central role. METHODS AND RESULTS: Ad.Trx1 was administered intramyocardially in nondiabetic and diabetic rats immediately after myocardial infarction. Ad.LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. Myocardial function was measured by echocardiography 30 days after the intervention. The Ad.Trx1-administered group exhibited reduced fibrosis, oxidative stress, and cardiomyocyte and endothelial cell apoptosis compared with the diabetic myocardial infarction group, along with increased capillary and arteriolar density. Western blot and immunohistochemical analysis demonstrated myocardial overexpression of thioredoxin-1, heme oxygenase-1, vascular endothelial growth factor, and p38 mitogen-activated protein kinase-beta, as well as decreased phosphorylated JNK and p38 mitogen-activated protein kinase-alpha, in the Ad.Trx1-treated diabetic group. Conversely, we observed a significant reduction in the expression of vascular endothelial growth factor in nondiabetic and diabetic animals treated with tin protoporphyrin (SnPP, a heme oxygenase-1 enzyme inhibitor), even after Ad.Trx1 therapy. Echocardiographic analysis after 4 weeks of myocardial infarction revealed significant improvement in myocardial functional parameters such as ejection fraction, fractional shortening, and E/A ratio in the Ad.Trx1-administered group compared with the diabetic myocardial infarction group. CONCLUSIONS: This study demonstrates for the first time that impairment of angiogenesis and myocardial dysfunction can be regulated by Ad.Trx1 gene therapy in streptozotocin-induced diabetic rats subjected to infarction.

Thioredoxin-1 gene delivery induces heme oxygenase-1 mediated myocardial preservation after chronic infarction in hypertensive rats.

BACKGROUND: Hypertension, the major risk factor for many cardiovascular diseases, is a result of multiple causes along with excessive generation of reactive oxygen species (ROS) resulting in imbalance of redox status. METHODS: In this study, we investigated the therapeutic potential of Adenoviral-Thioredoxin-1 (Adeno-Trx-1) in spontaneous hypertensive rats (SHRs) at a dosage of 1 x 10(9) pfu. The rats were assigned as normotensive Wistar-Kyoto (WKY), SHR, SHR + Adeno-Lac-Z (SHRLac-Z), and SHR + Adeno-Trx-1 (SHRTrx-1). Echo-guided injection of adeno virus was done 48 h before permanent myocardial infarction (MI) by left anterior descending coronary artery (LAD) occlusion. RESULTS: Decreased infarct size (52 +/- 4.1% vs. 67 +/- 6.1%), number of apoptotic cardiomyocytes (161 +/- 14.8 vs. 240 +/- 22.2), left ventricular inner diameter (7 +/- 0.33 vs. 9 +/- 0.46 mm), increased ejection fraction (52 +/- 6.3 vs. 42 +/- 3.3%), and fractional shortening (28 +/- 1.8 vs. 22 +/- 2.04 %) was observed in the SHRTrx-1 compared to SHR. Western Blot and immunohistochemical analysis demonstrated increased expression of Trx-1, HO-1, and Bcl-2 in the SHRTrx-1 compared to SHR. In addition, increased HO-1 activity was also observed in SHRTrx-1 as compared to SHR and SHRLac-Z groups. CONCLUSION: Our study demonstrates that the cardioprotective effect of Adeno-Trx-1 gene therapy in SHR is Trx-1/HO-1/Bcl-2 mediated and may represent future target to develop therapy against hypertension associated cardiac failure.

Strategic targets to induce neovascularization by resveratrol in hypercholesterolemic rat myocardium: role of caveolin-1, endothelial nitric oxide synthase, hemeoxygenase-1, and vascular endothelial growth factor.

Endothelial dysfunction and impaired angiogenesis constitute a hallmark of hypercholesterolemia. This study was designed to examine the effects of resveratrol, an antioxidant with lipid-lowering properties similar to those of statins, on neovascularization along with caveolar interaction with proangiogenic molecules in hypercholesterolemic rats. Animals were divided into: rats maintained on a normal diet (control group); rats maintained on a 5% high-cholesterol diet for 8 weeks (HC group); and rats maintained on a 5% high-cholesterol diet for 8 weeks and administered resveratrol (20 mg/kg) orally for 2 weeks (HCR group). Myocardial infarction was induced by ligating the left anterior descending artery. Herein we examined a novel method for stimulating myocardial angiogenesis by pharmacological preconditioning with resveratrol at both the capillary and arteriolar levels and the potential role of hemeoxygenase-1, endothelial nitric oxide synthase and caveolin-1 in mediating such a response. We also investigated the functional relevance of such treatment by assessing whether the induced neovascularization can help preserve left ventricle-contractile functional reserve in the setting of a chronic hypercholesterolemic condition. Four weeks after sham surgery and left anterior descending artery occlusion, rats underwent echocardiographic evaluation, which revealed improvement in ejection fraction and fractional shortening in the HCR group compared with the HC group. Left ventricular tissue sections displayed increased capillary and arteriolar density in the HCR group compared with the HC group. Western blot analysis revealed downregulation of vascular endothelial growth factor and hemeoxygenase-1 and increased association of caveolin-1 eNOS in the HC group, decreasing the availability of eNOS to the system; which was reversed with resveratrol treatment in the HCR group. This study was further validated in cardiac-specific hemeoxygenase-1-overexpressed mice assuming molecular cross-talk between the targets. Hence, our data identified potential regulators that primarily attenuate endothelial dysfunction by resveratrol therapy in hypercholesterolemic myocardium.