A retrospective analysis of anticoagulant safety among heart transplant recipients undergoing endomyocardial biopsy.

BACKGROUND: Transvenous endomyocardial biopsy is an invasive procedure which is used to diagnose rejection following an orthotopic heart transplant. Endomyocardial biopsy is widely regarded as low risk with all-cause complication rates below 5% in most safety studies. Following transplant, some patients require therapeutic anticoagulation. It is unknown whether anticoagulation increases endomyocardial biopsy bleeding risk. METHODS: Records from 2061 endomyocardial biopsies performed for post-transplant rejection surveillance at our institution between November 2016 and August 2022 were reviewed. Bleeding complications were defined as vascular access-related hematoma or bleeding, procedure-related red blood cell transfusion, and new pericardial effusion. Relative risk and small sample-adjusted 95% confidence interval was calculated to investigate the association between bleeding complications and anticoagulation. RESULTS AND CONCLUSIONS: The overall risk of bleeding was 1.2% (25/2061 cases). There was a statistically significant increase in bleeding among patients on intravenous (RR 4.46, CI 1.09-18.32) but not oral anticoagulants (RR .62, CI .15-2.63) compared to patients without anticoagulant exposure. There was a trend toward increased bleeding among patients taking warfarin with INR ≥ 1.8 (RR 3.74, CI .90-15.43). Importantly, no bleeding events occurred in patients taking direct oral anticoagulants such as apixaban. Based on these results, intravenous rather than oral anticoagulation was associated with a significantly higher risk of bleeding complications following endomyocardial biopsy.

Back to the basics: The need for an etiological classification of chronic heart failure.

The left ventricular (LV) ejection fraction (LVEF), despite its severe limitations, has had an epicentral role in heart failure (HF) classification, management, and risk stratification for decades. The major argument favoring the LVEF based HF classification has been that it defines groups of patients in which treatment is effective. However, this reasoning has recently collapsed, since medical treatment with neurohormonal inhibitors, has proved beneficial in most HF patients regardless of the LVEF. In addition, there has been compelling evidence, that the LVEF provides poor guidance for device treatment of chronic HF (implantation of cardioverter defibrillator, cardiac resynchronization therapy) since sudden cardiac death may occur and cardiac dyssynchronization may be disastrous in all HF patients. The same holds true for LV assist device implantation, in which the LVEF has been used as a surrogate for LV size. In this review article we update the evidence questioning the use of LVEF-based HF classification and argue that guidance of chronic HF treatment should transition to more contemporary concepts. Specifically, we propose an etiologic chronic HF classification predominantly based on epidemiological data, which will be foundational for further higher resolution phenotyping in the emerging era of precision medicine.

Acute mitral regurgitation with and without acute heart failure.

Acute severe mitral regurgitation (MR) is rare, but often leads to cardiogenic shock, pulmonary edema, or both. Most common causes of acute severe MR are chordae tendineae (CT) rupture, papillary muscle (PM) rupture, and infective endocarditis (IE). Mild to moderate MR is often seen in patients with acute myocardial infarction (AMI). CT rupture in patients with floppy mitral valve/mitral valve prolapse is the most common etiology of acute severe MR today. In IE, native or prosthetic valve damage can occur (leaflet perforation, ring detachment, other), as well as CT or PM rupture. Since the introduction of percutaneous revascularization in AMI, the incidence of PM rupture has substantially declined. In acute severe MR, the hemodynamic effects of the large regurgitant volume into the left atrium (LA) during left ventricular (LV) systole, and in turn back into the LV during diastole, are profound as the LV and LA have not had time to adapt to this additional volume. A rapid, but comprehensive evaluation of the patient with acute severe MR is essential in order to define the underline cause and apply appropriate management. Echocardiography with Doppler provides vital information related to the underlying pathology. Coronary arteriography should be performed in patients with an AMI to define coronary anatomy and need for revascularization. In acute severe MR, medical therapy should be used to stabilize the patient before intervention (surgery, transcatheter); mechanical support is often required. Diagnostic and therapeutic steps should be individualized, and a multi-disciplinary team approach should be utilized.

Percutaneous coronary intervention in patients with cancer using bare metal stents compared to drug-eluting stents.

Background: Management of coronary artery disease (CAD) is unique and challenging in cancer patients. However, little is known about the outcomes of using BMS or DES in these patients. This study aimed to compare the outcomes of percutaneous coronary intervention (PCI) in cancer patients who were treated with bare metal stents (BMS) vs. drug-eluting stents (DES). Methods: We identified cancer patients who underwent PCI using BMS or DES between 2013 and 2020. Outcomes of interest were overall survival (OS) and the number of revascularizations. The Kaplan-Meier method was used to estimate the survival probability. Multivariate Cox regression models were utilized to compare OS between BMS and DES. Results: We included 346 cancer patients who underwent PCI with a median follow-up of 34.1 months (95% CI, 28.4-38.7). Among these, 42 patients were treated with BMS (12.1%) and 304 with DES (87.9%). Age and gender were similar between the BMS and DES groups (p = 0.09 and 0.93, respectively). DES use was more frequent in the white race, while black patients had more BMS (p = 0.03). The use of DES was more common in patients with NSTEMI (p = 0.03). The median survival was 46 months (95% CI, 34-66). There was no significant difference in the number of revascularizations between the BMS and DES groups (p = 0.43). There was no significant difference in OS between the BMS and DES groups in multivariate analysis (p = 0.26). In addition, independent predictors for worse survival included age > 65 years, BMI ≤ 25 g/m2, hemoglobin level ≤ 12 g/dL, and initial presentation with NSTEMI. Conclusions: In our study, several revascularizations and survival were similar between cancer patients with CAD treated with BMS and DES. This finding suggests that DES use is not associated with an increased risk for stent thrombosis, and as cancer survival improves, there may be a more significant role for DES.

Floppy mitral valve/mitral valve prolapse and sudden cardiac death.

It is well appreciated today that sudden cardiac death (SCD) occurs in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP) without significant mitral regurgitation . Data from studies most likely represent a heterogeneous population and probably underestimate the true incidence of SCD in this group of patients. SCD in patients with FMV/MVP occurs mostly in young individuals without comorbidities. Over the last decade, the phenotypic expression of patients with FMV/MVP at risk for SCD (bileaflet prolapse, redundant mitral leaflets, symptomatic young women) have been defined, possible pathophysiologic mechanisms leading to SCD have been proposed, and appropriate steps to prevent the catastrophic event, though in evolution, have been suggested. In this review, state-of-the-art knowledge related to SCD in patients with FMV/MVP is summarized.

Effect of mitral valve transcatheter edge-to-edge repair on indices of left atrial performance in chronic mitral regurgitation.

INTRODUCTION: Effect of transcatheter edge-to-edge repair (TEER) using MitraClip in patients with mitral regurgitation (MR) on left atrial (LA) kinetic energy (LAKE), an index of LA work, and LA strain, a measure of LA performance, have not been well defined. METHODS: Patients with chronic primary or secondary 3+ or 4+ MR were analyzed pre- and post-TEER using MitraClip. LAKE was determined by echocardiography using LA stroke volume and A-wave velocity. Peak atrial longitudinal strain (PALS), peak atrial strain in early diastole, and peak atrial contraction strain (PACS) were obtained by speckle tracking echocardiography. RESULTS: Thirty-nine patients undergoing TEER with MitraClip were screened, 12 met criteria for analysis (9 primary and 3 secondary MR). Compared to pre-TEER, there was a significant increase post-TEER in LAKE (71.0 ± 64.1 vs. 177.5 ± 167.9 dyne·cm·103 , respectively; p = .008) and Doppler transmitral A-wave velocity (87.8 ± 41.4 vs. 138.5 ± 43.7 cm/s, respectively; p < .001); LA stroke volume did not change significantly. Mitral valve mean gradient significantly increased post-TEER compared to pre-TEER (5.7 ± 2.1 vs. 3.3 ± 2.1 mmHg, respectively; p = .01). There was a trend toward decrease in PALS post-TEER compared to pre-TEER (16.2 ± 4.8 vs. 20.7 ± 9.9%, respectively; p = .05). Peak atrial strain in early diastole significantly decreased post-TEER compared to pre-TEER (7.2 ± 3.0 vs. 14.1 ± 7.2%; respectively, p < .001), while PACS did not significantly change (9.1 ± 3.5 vs. 6.7 ± 5.2%, respectively; p = .07). CONCLUSION: In patients with chronic MR, LAKE increases after TEER with MitraClip driven by an increase in LA emptying velocities. Changes were also seen in LA strain with MitraClip. These procedurally induced changes due to mild mitral stenosis may have clinical implications.

Concomitant anaortic OPCAB and transfemoral TAVR for high-risk patients: A case series.

BACKGROUND: Combined on-pump coronary artery bypass (ONCAB) and surgical aortic valve replacement (SAVR) is the treatment of choice for concomitant severe aortic stenosis and coronary artery disease not amenable to percutaneous coronary intervention. Extensive aortic calcification and atheromatous disease may prohibit cardiopulmonary bypass and aortic cross-clamping. In these cases, anaortic off-pump coronary artery bypass (OPCAB) is a Class I (EACTS 2018) and Class IIA (AHA 2021) indication for surgical coronary revascularization. Transcatheter aortic valve replacement (TAVR) has similar benefits when compared with SAVR for this population (Partner 2 & 3). Herewith we describe a case series of concomitant Anaortic OPCAB and TAVR via the transfemoral approach for patients with coronary artery and valve disease considered too high risk for traditional coronary artery bypass grafting and SAVR due to severe aortic disease. METHODS/RESULTS: Eight patients underwent anaortic OPCAB and transfemoral TAVR during the same anesthetic in a hybrid operating room. Seven patients with multivessel disease had anaortic OPCAB via a sternotomy using composite grafts, one patient with LAD disease had anaortic OPCAB using a Da Vinci-assisted MIDCAB approach. All patients then had an Edwards Sapien 3 TAVR placed percutaneously via the common femoral artery. There was no 30 mortality or CVA in the series and all patients were discharged to home or a rehabilitation facility on Day 4-13. CONCLUSIONS: Combined anaortic OPCAB and transfemoral TAVR is a safe and feasible approach to treating concomitant extensive coronary artery disease and severe aortic stenosis. The aortic no-touch technique provides benefits in the elderly high-risk patients by reducing the risk of postoperative myocardial infarction and cerebrovascular stroke.

The Interventricular Septum: Structure, Function, Dysfunction, and Diseases.

Vertebrates developed pulmonary circulation and septated the heart into venous and arterial compartments, as the adaptation from aquatic to terrestrial life requires more oxygen and energy. The interventricular septum (IVS) accommodates the ventricular portion of the conduction system and contributes to the mechanical function of both ventricles. Conditions or diseases that affect IVS structure and function (e.g., hypertrophy, defects, other) may lead to ventricular pump failure and/or ventricular arrhythmias with grave consequences. IVS structure and function can be evaluated today using current imaging techniques. Effective therapies can be provided in most cases, although definitions of underlying etiologies may not always be easy, particularly in the elderly due to overlap between genetic and acquired causes of IVS hypertrophy, the most common being IVS abnormality. In this review, state-of-the-art information regarding IVS morphology, physiology, physiopathology, and disease is presented.

Comparison of Catheterization Versus Echocardiographic-Based Gradients in Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Implantation.

OBJECTIVES: In patients with transcatheter aortic valve implantation (TAVI), accurate assessment of gradients is important to assess valve function and durability, which drives clinical decision-making. We sought to evaluate discrepancies in aortic valve mean gradients with balloon-expandable and self-expanding TAVI. METHODS: We retrospectively reviewed 507 patients that underwent TAVI and compared mean gradients by catheterization to transthoracic Doppler echocardiography. RESULTS: Mean gradients by Doppler in balloon-expandable (11.0 ± 5.8 mm Hg) and self-expanding devices (8.7 ± 4.5 mm Hg) were significantly higher than catheterization (3.2 ± 4.0 mm Hg vs 3.5 ± 4.1 mm Hg, respectively; P<.001). In a subgroup analysis of skirted valves, Doppler gradients in balloon-expandable (9.8 ± 4.4 mm Hg) and self-expanding devices (8.6 ± 5.1 mm Hg) were significantly higher than catheterization (3.5 ± 4.1 mm Hg vs 4.2 ± 4.8 mm Hg, respectively; P<.001). When the effect of valve size on gradients was analyzed, Doppler gradients were significantly higher than catheterization for all comparisons. When indexed for valve size, patients with large aortas who received a balloon-expandable TAVI had greater pressure differential than those who received a self-expanding TAVI (8.24 ± 0.46 mm Hg vs 5.16 ± 0.66 mm Hg; P<.001). This trend was not seen in patients with a small aorta-to-valve index. CONCLUSION: Following TAVI, aortic valve mean gradients acquired by Doppler were higher than catheterization and the discrepancy was more pronounced in balloon-expandable than self-expanding prostheses. These differences persist in skirted valves and across valve sizes. These observations may reflect periprocedural hemodynamic changes, differences between prosthetic flow acceleration, and/or pressure recovery.

Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art.

The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to genetic testing guided therapy. In addition, assays of platelet function and biochemistry have provided insight into our understanding of the efficacy of "antiplatelet" therapy, identifying patients with high or low platelet reactivity on P2Y12 therapy. Despite the data, the implementation of these testing modalities has not gained mainstream adoption across hospital systems. Given differences in potency between the three clinically available P2Y12 inhibitors, the balance between thrombotic and bleeding complications must be carefully considered, especially for the large proportion of patients at higher risk for bleeding. Here we review the current data for genetic and functional testing, risk assessment strategies, and guidelines for P2Y12 inhibitors guided therapy.

Effects of MitraClip Therapy on Mitral Flow Patterns and Vortex Formation: An In Vitro Study.

MitraClip transcatheter edge-to-edge repair is used to treat mitral regurgitation (MR). While MR is reduced, diastolic left ventricular flows are altered. An in vitro left heart simulator was used to assess a porcine mitral valve in the native, MR, and MR plus MitraClip cases. Velocity, vorticity, and Reynolds shear stress (RSS) were quantified by particle image velocimetry. Peak velocity increased from 1.20 m/s for native to 1.30 m/s with MR. With MitraClip, two divergent jets of 1.18 and 0.61 m/s emerged. Higher vorticity was observed with MR than native and lessened with MitraClip. MitraClip resulted in shear layer formation and downstream vortex formation. Native RSS decreased from 33 Pa in acceleration to 29 Pa at peak flow, then increased to 31 Pa with deceleration. MR RSS increased from 27 Pa in acceleration to 40 Pa at peak flow to 59 Pa during deceleration. MitraClip RSS increased from 79 Pa in acceleration to 162 Pa during peak flow, then decreased to 45 Pa during deceleration. After MitraClip, two divergent jets of reduced velocity emerged, accompanied by shear layers and recirculation. Chaotic flow developed, resulting in elevated RSS magnitude and coverage. Findings help understand consequences of MitraClip on left ventricular flow dynamics.

Right Ventricular Myocardial Infarction Complicated by Cardiac Arrest: Utilization of Extracorporeal Membrane Oxygenation.

A 44-year-old male with an out-of-hospital cardiac arrest due to an acute left ventricular (LV) inferoposterior wall myocardial infarction (MI) involving the right ventricle (RV) is presented. This case highlights the challenges in the management of patients with cardiac arrest, indications for use of ventricular assist devices, potential effects of LV assist devices on the RV in the setting of RV MI, and culprit versus complete coronary artery revascularization in these patients.

Cardiovascular Disease, Cancer, and Multimorbidity Interactions: Clinical Implications.

BACKGROUND: With the aging population, the frequency of cardiovascular disease (CVD), cancer, and other morbid conditions is increasing dramatically. In addition, one disease may affect the other leading to a vicious cycle. SUMMARY: With aging, the function of organs and systems of the human body declines including the immune system resulting in a diminished response to various pathogens and a chronic inflammatory process; these changes, in addition to other risk factors, contribute to the development of multiple morbid conditions including CVD and cancer. Multimorbidity in the elderly has become the rule rather than the exception today. Further, this association between CVD and cancer, at least partially, is explained by both diseases sharing common risk factors and from accelerated vascular aging due to cancer and its associated therapies. Multiple studies have shown that the incidence of cancer is much higher in patients with CVD compared to the general population. These associations among CVD, cancer, and their connection to systems of the human body provide an opportunity for novel therapies. Development of new drugs should be addressed to focus on multiple systems and not just only to one disease. Further, collecting information from registries and processing large amounts of data using artificial intelligence may assist the clinician when treating an individual patient in the future. KEY MESSAGES: As the aging population increases, CVD, cancer, and multimorbidity will continue to constitute a major health problem in the years to come. The physician who is taking care of such a patient, in addition to knowledge, requires clinical wisdom, clinical experience, and common sense in order to apply the continuous evolving knowledge to the individual patient.

Multiple MitraClips: The balancing act between pressure gradient and regurgitation.

OBJECTIVE: Transcatheter mitral valve repair with the MitraClip is used for the symptomatic management of mitral regurgitation (MR). The challenge is reducing MR while avoiding an elevated mitral valve gradient (MVG). This study assesses how multiple MitraClips used to treat MR can affect valve performance. METHODS: Six porcine mitral valves were assessed using an in vitro left heart simulator in the native, moderate-to-severe MR, and severe MR cases. MR cases were tested in the no-MitraClip, 1-MitraClip, and 2-MitraClip configurations. Mitral regurgitant fraction (MRF), MVG, and effective orifice area (EOA) were quantified. RESULTS: Native MRF, MVG, and EOA were 14.22%, 2.59 mm Hg, and 1.64 cm2, respectively. For moderate-to-severe MR, MRF, MVG, and EOA were 34.07%, 3.31 mm Hg, and 2.22 cm2, respectively. Compared with the no-MitraClip case, 1 MitraClip decreased MRF to 18.57% (P < .0001) and EOA to 1.50 cm2 (P = .0002). MVG remained statistically unchanged (3.44 mm Hg). Two MitraClips decreased MRF to 14.26% (P < .0001) and EOA to 1.36 cm2 (P = .0001). MVG remained unchanged (3.29 mm Hg). For severe MR, MRF, MVG, and EOA were 59.79%, 4.98 mm Hg, and 2.73 cm2, respectively. Compared with the no-MitraClip case, 1 MitraClip decreased MRF to 30.72% (P < .0001) and EOA to 1.82 cm2 (P < .0001); MVG remained unchanged (4.03 mm Hg). MVG remained statistically unchanged. Two MitraClips decreased MRF to 23.10% (P < .0001) and EOA to 1.58 cm2 (P < .0001); MVG remained statistically unchanged (3.82 mm Hg). Both MR models yielded no statistical difference between 1 and 2 MitraClips. CONCLUSIONS: There is limited concern regarding elevation of MVG when reducing MR using 1 or 2 MitraClips, although 2 MitraClips did not significantly continue to reduce MRF.

Black lives matter in the cath lab, too! A proposal for the interventional cardiology community to counteract bias and racism.

Structural racism in the United States underlies racial disparities in the criminal justice system, in the healthcare system generally, and with regards to the COVID-19 pandemic. In the year 2020, these inequities combined and magnified to such a degree that it left Black Americans and physicians caring for them questioning how much Black lives matter. Academic medical centers and the major cardiology organizations responded to a global call to end racism with bold statements and initiatives. Interventional cardiologists utilize advanced equipment to mechanically treat a wide spectrum of heart problems, yet this technology has not been applied in an equitable manner. Interventional therapies are often underutilized in Blacks, exacerbating healthcare disparities and contributing to the excess cardiovascular morbidity and mortality in these communities. Racial bias, whether intentional, unconscious, systemic, or at the individual level, plays a role in these disparities. Many in the interventional cardiology community aspire to take intentional steps to reduce the impact of bias and racism in our specialty. We discuss several proposals here and provide a "report card" for interventional programs to perform a self-assessment.

De novo Drug Delivery Modalities for Treating Damaged Hearts: Current Challenges and Emerging Solutions.

Cardiovascular disease (CVD) is the leading cause of mortality, resulting in approximately one-third of deaths worldwide. Among CVD, acute myocardial infarctions (MI) is the leading cause of death. Current treatment modalities for treating CVD have improved over the years, but the demand for new and innovative therapies has been on the rise. The field of nanomedicine and nanotechnology has opened a new paradigm for treating damaged hearts by providing improved drug delivery methods, specifically targeting injured areas of the myocardium. With the advent of innovative biomaterials, newer therapeutics such as growth factors, stem cells, and exosomes have been successfully delivered to the injured myocardial tissue, promoting improvement in cardiac function. This review focuses on three major drug delivery modalities: nanoparticles, microspheres, and hydrogels, and their potential for treating damaged hearts following an MI.