Afterload mismatch after transcatheter mitral valve repair with MitraClip for degenerative mitral regurgitation in acute cardiogenic shock.

Acute afterload mismatch after surgery for mitral regurgitation (MR) with transient left ventricular dysfunction is well known, but not described after transcatheter mitral valve repair with MitraClip, except in functional MR and cardiomyopathy. MitraClip to manage acute severe MR and cardiogenic shock has also been rarely reported. We report here a 77-year-old female who presented with acute severe degenerative MR from a flail posterior leaflet, with cardiogenic shock requiring intra-aortic balloon pump support. She was medically stabilized and underwent successful MitraClip repair with mild residual MR, but developed acute afterload mismatch and severe left ventricular dysfunction and shock 24 hr after her procedure. Patient was medically managed with intra-aortic balloon pump and inotropic support. She subsequently fully recovered with normal ventricular function and was discharged after 14 days. Patient remained asymptomatic in NYHA I functional class 9 months after MitraClip repair, with mild residual MR and normal ventricular function. MitraClip repair in patients with acute severe degenerative MR and cardiogenic shock is a less invasive and potentially safer alternative to open surgery, but acute afterload mismatch may occur and requires prompt diagnosis and management for a successful outcome. © 2017 Wiley Periodicals, Inc.

Continuous invasive hemodynamic monitoring using steerable guide catheter to optimize mitraclip transcatheter mitral valve repair: A multicenter, proof-of-concept study.

OBJECTIVES: We report our multicenter experience on continuous hemodynamic monitoring using exclusively the steerable guide catheter (SGC) during MitraClip repair. BACKGROUND: Left atrial pressure (LAP) and V-wave are useful to evaluate MitraClip repair but no simple method of continuous monitoring exists. METHODS: From 11/2016 to 8/2017, 74 patients from four centers with symptomatic moderate-severe to severe mitral regurgitation (MR), underwent MitraClip NT repair with continuous hemodynamic monitoring via the SGC. Real-time LAP/V-wave changes were compared with transesophageal echocardiography (TEE). When mitral stenosis was suspected, transmitral gradients were verified by invasive hemodynamics. Clinical and echocardiographic outcomes were determined. RESULTS: Mean age was 78 ± 10 years and STS score 9.1 ± 11.0%. Pathology included leaflet prolapse/flail (45%), restriction (35%), and mixed (20%). Number of clips averaged 1.7 ± 0.7 per case. There was a significant reduction in LAP (21 ± 10 to 15 ± 7 mmHg, P < 0.0001) and V-wave(37 ± 19 to 24 ± 10 mmHg, P < 0.0001) post MitraClip, but the decrease was less in patients with atrial fibrillation (P < 0.05). Transmitral gradient significantly increased from 2.0 ± 1.2 to 4.0 ± 1.7 mmHg (P < 0.0001). Paradoxical increases in LAP and V-wave despite MR reduction were observed in three cases requiring MitraClip repositioning or retrieval to avoid stenosis. Follow-up averaged 5.0 ± 2.9 months and was 100% complete. KCCQ improvement was significant and MR reduction to <1+ was 67% and <2+ was 93% at 30 days. CONCLUSIONS: Continuous hemodynamic monitoring using the SGC complements TEE to assess and optimize MitraClip repair in real-time. Further validation is necessary but this feature may be part of future MitraClip and other transcatheter mitral repair systems.

Variations in Mitral Valve Leaflet and Scallop Anatomy on Three-Dimensional Transesophageal Echocardiography.

BACKGROUND: Textbook depictions of the mitral valve (MV) often illustrate it as composed of a single nonscalloped anterior leaflet, with the posterior leaflet having three symmetric and evenly spaced scallops. However, common variations in this anatomy have been noted in autopsy series for decades. Improved cardiac imaging with three-dimensional transesophageal echocardiography (TEE) now affords the ability to detect variations in scallop anatomy in vivo. The aims of this study were to catalog variations in mitral anatomy and to examine for association with mitral regurgitation in patients referred for clinical three-dimensional TEE. METHODS: Three-dimensional transesophageal echocardiographic images of the MV from 107 subjects were reviewed for MV variations. Three-dimensional analysis software was used to characterize mitral leaflet anatomy and assess the relative sizes of posterior leaflet scallops. RESULTS: Variations from the classic MV configuration were seen in 58.9%. Symmetric variations in the posterior leaflet (dominant P2 scallop, accessory P2 scallop, absent P2 scallop, and dichotomous P2 scallop) were seen in 33.6% of the study group. Asymmetric variants in the posterior leaflet (fused P1 and P2, fused P2 and P3, commissural scallop, accessory scallops, dichotomous P1 or P3, and dominant P2 or P3) were seen in 24.3%. Indentations or folds in the anterior leaflet were noted in 5.6%. Leaflet variations were not associated with patient demographics, indication for TEE, mitral regurgitation, mitral annular dimensions, or Carpentier class. CONCLUSIONS: Mitral leaflet morphologic variants were well characterized using three-dimensional TEE. Variants are common and were present with a frequency consistent with autopsy series. Mitral scallop variations were not associated with mitral regurgitation.

Pulmonary Artery Denervation as an Innovative Treatment for Pulmonary Hypertension With and Without Heart Failure.

Pulmonary hypertension (PH) is categorized into 5 groups based on etiology. The 2 most prevalent forms are pulmonary arterial hypertension (PAH) and PH due to left heart disease (PH-LHD). Therapeutic options do exist for PAH to decrease symptoms and improve functional capacity; however, the mortality rate remains high and clinical improvements are limited. PH-LHD is the most common cause of PH; however, no treatment exists and the use of PAH-therapies is discouraged. Pulmonary artery denervation (PADN) is an innovative catheter-based ablation technique targeting the afferent and efferent fibers of a baroreceptor reflex in the main pulmonary artery (PA) trunk and its bifurcation. This reflex is involved in the elevation of the PA pressure seen in PH. Since 2013, both animal trials and human trials have shown the efficacy of PADN in improving PAH, including improved hemodynamic parameters, increased functional capacity, decreased PA remodeling, and much more. PADN has been shown to decrease the rate of rehospitalization, PH-related complications, and death, and is an overall safe procedure. PADN has also been shown to be effective for PH-LHD. Additional therapeutic mechanisms and benefits of PADN are discussed along with new PADN techniques. PADN has shown efficacy and safety as a potential treatment option for PH.

Treatment of Peripheral Pulmonary Artery Stenosis.

Peripheral pulmonary artery stenosis (PAS) is an abnormal narrowing of the pulmonary vasculature and can form anywhere within the pulmonary artery tree. PAS is a congenital or an acquired disease, and its severity depends on the etiology, location, and number of stenoses. Most often seen in infants and young children, some symptoms include shortness of breath, fatigue, and tachycardia. Symptoms can progressively worsen over time as right ventricular pressure increases, leading to further complications including pulmonary artery hypertension and systolic and diastolic dysfunctions. The current treatment options for PAS include simple balloon angioplasty, cutting balloon angioplasty, and stent placement. Simple balloon angioplasty is the most basic therapeutic option for proximally located PAS. Cutting balloon angioplasty is utilized for more dilation-resistant PAS vessels and for more distally located PAS. Stent placement is the most effective option seen to treat the majority of PAS; however, it requires multiple re-interventions for serial dilations and is generally reserved for PAS vessels that are resistant to angioplasty.

Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare congenital arrhythmogenic disorder induced by physical or emotional stress. It mainly affects children and younger adults and is characterized by rapid polymorphic and bidirectional ventricular tachycardia. Symptoms can include dizziness, palpitations, and presyncope, which may progress to syncope, hypotonia, convulsive movements, and sudden cardiac death. CPVT is the result of perturbations in Ca ion handling in the sarcoplasmic reticulum of cardiac myocytes. Mutations in the cardiac ryanodine receptor gene and the calsequestrin isoform 2 gene are most commonly seen in familial CPVT patients. Under catecholaminergic stimulation, either mutation can result in an excess Ca load during diastole resulting in delayed after depolarization and subsequent arrhythmogenesis. The current first-line treatment for CPVT is ß-blocker therapy. Other therapeutic interventions that can be used in conjunction with ß-blockers include moderate exercise training, flecainide, left cardiac sympathetic denervation, and implantable cardioverter-defibrillators. Several potential therapeutic interventions, including verapamil, dantrolene, JTV519, and gene therapy, are also discussed.

A meta-analysis of 1-year outcomes of transcatheter versus surgical aortic valve replacement in low-risk patients with severe aortic stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) for the treatment symptomatic severe aortic stenosis (AS) is indicated in patients with intermediate or higher surgical risk. Latest trials showed TAVR, and surgical aortic valve replacement (SAVR) perform similarly at 1-year for the composite outcomes of mortality, stroke and rehospitalization. We performed a comprehensive meta-analysis to compare individual outcomes at 1-year for TAVR compared to SAVR in low-risk patients. METHODS: PubMed, Embase, and Cochrane central were searched for all the randomized controlled trials (RCTs) that reported 1-year comparative outcomes of TAVR and surgical aortic valve replacement (SAVR). Our conclusions are based upon the random-effects model using DerSimonian-Laird estimator. RESULTS: Data from 4 trials and 2887 randomized patients showed that TAVR had lower rates of all-cause mortality, cardiovascular mortality, and atrial fibrillation compared to SAVR at 1-year follow-up (P < 0.05 for all). Also, TAVR was also associated with a significantly higher risk of permanent pacemaker implantation and moderate-severe paravalvular leak (P < 0.05). CONCLUSIONS: The latest randomised trial data demonstrates that in short-term, TAVR is safe and effective in reducing all-cause mortality or stroke. Longer follow-up of RCTs is needed to determine the durability of clinical benefits in TAVR over SAVR in low-risk patients.

Survival and Right Ventricular Function After Surgical Management of Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is associated with high morbidity and mortality because of right ventricular (RV) failure. There is evidence suggesting surgical therapy (surgical embolectomy or venoarterial extracorporeal membrane oxygenation [ECMO]) is safe and effective. OBJECTIVES: The aim of this study was to assess the safety and efficacy of surgical management of acute PE. METHODS: Surgical embolectomy and/or venoarterial ECMO were compared, between 2005 and 2019, for massive PE (MPE) versus high-risk submassive PE (SMPE). RV recovery was defined as improvements in central venous pressure, pulmonary artery systolic pressure, RV/left ventricular ratio, and RV fractional area change. RESULTS: One hundred thirty-six patients with PE (92 with SMPE and 44 with MPE) were identified. Patients with MPE more often presented with syncope (59.1% [26 of 44] vs. 25.0% [23 of 92]; p = 0.0003), Glasgow Coma Scale score ≤4 (22.7% [10 of 44] vs. 0% [0 of 92]), and failed thrombolysis (18.2% [8 of 44] vs. 4.3% [3 of 92]; p = 0.008). Pre-operative cardiopulmonary resuscitation occurred in 43.2% of patients with MPE (19 of 44). Most patients with SMPE were treated with embolectomy (98.9% [91 of 92]), while ECMO was used more in those with MPE (ECMO in 40.9% [18 of 44], embolectomy in 59.1% [26 of 44]). RV function improved as measured by central venous pressure (from 23.4 ± 4.9 to 10.5 ± 3.1 mm Hg), pulmonary artery systolic pressure (from 60.6 ± 14.2 to 33.8 ± 10.7 mm Hg), RV/left ventricular ratio (from 1.19 ± 0.33 to 0.87 ± 0.23; p < 0.005), and fractional area change (from 26.8 to 41.0; p < 0.005). Mortality was 4.4% (6 of 136; SMPE, 1.1% [1 of 92]; MPE, 11.6% [5 of 44]). Subgroup analysis showed morbidity and mortality were highly associated with pre-operative cardiopulmonary resuscitation. CONCLUSIONS: Surgical management of patients with MPE and high-risk SMPE is safe and highly effective at achieving RV recovery.

The left ventricular ejection fraction: new insights into an old parameter.

Accurate evaluation of cardiac function has become increasingly important as the treatment of cardiac disease has become more complex. At the same time, technological advances allow greater accuracy and precision in cardiac measurements. Measurement of left ventricular ejection fraction (LVEF) has been a pillar of cardiac evaluation. Several noninvasive modalities are available to assess LVEF; each has advantages and limitations. This review examines various modalities used to measure LVEF and focuses on the relative strengths and weaknesses of each modality. In some clinical settings, however, LVEF may be too insensitive to convey subtle changes in LV contractility. In certain clinical situations, use of LVEF may be an insufficient measure of left ventricular systolic function. Global longitudinal strain is one such parameter that has shown promise for detecting subtle reductions in left ventricular contractility in subjects with chemotherapy-induced cardiotoxicity.

Interventional therapies for relief of obstruction in hypertrophic cardiomyopathy: discussion and proposed clinical algorithm.

Hypertrophic cardiomyopathy (HCM), a disease formerly thought rare in clinical practice, is now believed to affect as many as 1 in 300 individuals, regardless of race or gender. Rising awareness, coupled with advanced imaging and the development of dedicated HCM centers of excellence, has led to more patients coming to clinical presentation. While some are diagnosed at a young age, others are diagnosed in middle age or well into advanced age. Unfortunately, many such patients have progressed clinically to overt heart failure, or have some combination of advanced symptoms including dyspnea, angina, pre-syncope or syncope, palpitations, and edema. Anatomic subsets, including those with mid-ventricular obstruction or apical disease, with or without apical aneurysm, have also been seen in increasing frequency. Fortunately, both percutaneous and surgical invasive options are available across the spectrum of disease severity and anatomy, with outcomes continuing to improve as the techniques and experience evolve. Advances in both approaches allow targeted and individualized treatment of the majority of these patients. This review will focus on interventional approaches to relief of obstruction, and will provide a current clinical algorithm from our center for determining when an interventional approach may be recommended or optimal over a surgical approach, and vice versa.

Novel predictors of mild paravalvular aortic regurgitation in SAPIEN 3 transcatheter aortic valve implantation.

AIMS: Paravalvular leak (PVL) remains an important issue in TAVI. The Edwards SAPIEN 3 (S3) valve has reduced PVL but in up to one third of patients mild leak remains. Our study aimed to identify predictors of mild PVL after TAVI with the S3 valve. METHODS AND RESULTS: From October 2015 to May 2017, 122 consecutive patients underwent S3 TAVI for symptomatic severe aortic stenosis. Thirty-three patients with mild PVL on transthoracic echocardiography at 30-day follow-up were compared to 89 with none/trace PVL. Thirty-day mortality was 2.5% (n=3), with zero stroke and major vascular complications. There were no differences between the two groups in patient characteristics, annular and left ventricular outflow tract (LVOT) sizing, distribution and severity of annular calcification, valve implantation technique, post-dilatation and implant depth. Mild PVL was associated with higher annular eccentricity (p=0.04) and moderate-severe LVOT calcification (p=0.03). Independent predictors of mild PVL were LVOT eccentricity (OR 1.05 per % ellipticity, 95% CI: 1.02-1.09, p=0.005), discordant sizing (OR 3.08, 95% CI: 1.20-7.90, p=0.02) and three-leaflet calcification (OR 13.3, 95% CI: 2.66-66.7, p=0.002). CONCLUSIONS: LVOT eccentricity and discordant sizing predict PVL after S3 TAVI. Further studies are needed to understand their mechanism and significance.

Echocardiographic evaluation of the right ventricle: Clinical implications.

Interest in evaluation of the right ventricle (RV) has increased recently. With the growth of new echocardiographic techniques and technology, there has been a corresponding increase in the ability to evaluate the RV, both qualitatively and quantitatively. Older echocardiographic techniques, such as right ventricular fractional area of change, tricuspid annular plane systolic excursion, and tissue S', and newer echocardiographic techniques including 3-dimensional evaluation and global longitudinal strain, can improve our evaluation of RV function. These techniques provide both diagnostic and prognostic data on a large variety of clinical diseases including pulmonary hypertension and congestive heart failure. With the continuing and exponential advances in technology, echocardiography is well poised to become the primary modality to evaluate the RV.

Echocardiography in the Evaluation of Pulmonary Embolism.

Pulmonary embolism is a major cause of mortality. Acute pulmonary embolism also encompasses a wide clinical spectrum of severity, ranging from asymptomatic silent disease to hemodynamic instability and shock. Echocardiography is a useful modality to improve treatment strategies for pulmonary embolus. Echocardiography plays a role in risk stratification at the time of diagnosis. The evaluation of the right ventricle (RV) has evolved over time. RV variables evaluated by echocardiography include RV size, RV/left ventricular ratio, RV fractional area of change, tricuspid annular plane systolic excursion, RV systolic pressure, and RV Tei index. It has also been used in determining treatment strategies and following the success of treatment. Multiple echocardiographic criteria have been studied to improve risk stratification and outcomes from pulmonary embolism. Further studies are needed to assess the appropriate quantitative echocardiographic parameters.

First percutaneous Micra leadless pacemaker implantation and tricuspid valve repair with MitraClip NT for lead-associated severe tricuspid regurgitation.

AIMS: Pacemaker lead-associated severe tricuspid regurgitation (TR) can lead to right heart failure and poor prognosis. Surgery in these patients carries significant morbidities. We describe a successful treatment of symptomatic severe TR by leadless pacemaker implantation followed by tricuspid valve (TV) repair with the MitraClip NT. METHODS AND RESULTS: A 71-year-old frail female with poor functional status, chronic atrial fibrillation and permanent pacemaker implantation in 2012 presented with symptomatic moderate-severe mitral regurgitation (MR) and severe TR with the pacemaker lead as the culprit. She was deemed extreme risk for double valve surgery and, because of her pacemaker dependency, the decision was to stage her interventions first with transcatheter mitral repair, then laser lead extraction and leadless pacemaker implantation to free the TV from tethering, then TV repair. An obstructive LAD lesion was identified and treated during mitral repair with the MitraClip NT. The Micra leadless pacemaker implantation and subsequent TV repair with the MitraClip NT were successful and the patient's MR improved to mild and TR to moderate, respectively. CONCLUSIONS: We report here a first successful transcatheter strategy to treat lead-associated severe TR by leadless pacemaker and MitraClip. Removing the pacemaker lead relieved leaflet tethering and improved the reparability of the TV.

Yield of transesophageal echocardiography for nonbacterial thrombotic endocarditis and other cardiac sources of embolism in cancer patients with cerebral ischemia.

Cerebrovascular events occur frequently in patients who succumb to cancer, and nonbacterial thrombotic endocarditis (NBTE) is a frequent postmortem finding in these patients. Despite the excellent diagnostic accuracy of transesophageal echocardiography (TEE) for cardiac sources of cerebral embolism, however, the prevalence of NBTE and other cardioembolic sources in patients with cancer and cerebral ischemia has not been investigated using this modality. This study examined the frequency of cardioembolic findings in consecutive patients with cancer referred to our institution for TEE evaluation of cerebrovascular events. The study cohort comprised 51 patients, of whom 18% had marantic vegetations, and 47% and 55% of whom had definite and definite or probable cardiac sources of embolism, respectively. The present study documents, for the first time, a high frequency of marantic endocarditis and other cardioembolic sources in patients with cancer and cerebrovascular events selected for TEE. This finding has important implications for evaluation and management in this patient population.

Neurogenic stress cardiomyopathy associated with subarachnoid hemorrhage.

Cardiac manifestations are recognized complications of subarachnoid hemorrhage. Neurogenic stress cardiomyopathy is one complication that is seen in acute subarachnoid hemorrhage. It can present as transient diffuse left ventricular dysfunction or as transient regional wall motion abnormalities. It occurs more frequently with neurologically severe-grade subarachnoid hemorrhage and is associated with increased morbidity and poor clinical outcomes. Managing this subset of patients is challenging. Early identification followed by a multidisciplinary team approach can potentially improve outcomes.

Transcatheter aortic valve replacement: current developments, ongoing issues, future outlook.

Since the first clinical implantation in 2002, transcatheter aortic valve implantation or transcatheter aortic valve replacement (TAVR) has become an established therapy in the treatment of symptomatic severe aortic stenosis in patients deemed too high risk for surgical aortic valve replacement. With over 50,000 implants performed in more than 40 countries, a large amount of clinical data have emerged in this rapidly growing field. Careful patient selection, systematic risk stratification, optimal valve sizing, meticulous procedural techniques, and complications management are all important elements to achieve good outcomes. However, several critical issues exist with TAVR that need to be addressed before it can become more widely adopted. Quality of life improvement and cost-effectiveness of TAVR, when compared to surgical aortic valve replacement, remain uncertain in lower risk patients. Stroke, paravalvular leak, vascular complication, bleeding, and heart block represent only a few of the key concerns in this therapy. Valve-in-valve procedures are becoming a novel application of transcatheter heart valve in the treatment of a degenerated bioprosthesis, and next generation heart valves that address some of these ongoing issues are currently under evaluation. Future prospective studies will allow us to refine this therapy and optimize outcomes in this high-risk patient population.

Robust ability of IFN-gamma to upregulate class II MHC antigen expression in tumor bearing rat brains.

T cells are attractive for delivering therapy to brain tumor, especially disseminated micro-tumor. However, to trigger effector function, tumor antigen must be re-presented to T cells, via major histocompatibility complex (MHC) proteins, at the tumor site. In normal brain, MHC+ antigen-presenting cells (APC) are rare, but abundant after gamma interferon (IFN-gamma) injection. Here we studied tumor-bearing brains. IFN-gamma (or buffer) was injected stereotactically into brains with established tumors from a panel of immunologically varied glioma cell lines, some expressing b-galactosidase as a micro-tumor marker. Four days later, cryostat sections were stained for tumor and MHC proteins. In phosphate-buffered saline-injected controls, class II MHC+ potential APC (microglia, macrophages) were seen only at (some) tumor sites. In rats that received IFN-gamma, class II+ potential APC were widespread, including all actual and potential micro-tumor sites and all tumor-free areas. In the same slides, neither class I nor class II MHC antigen was detected in neural cells or most tumor cells. This MHC pattern favors indirect re-presentation of tumor antigen, by tumor-adjacent APC. The robust response to IFN-gamma might also be exploited in other ways: activated microglia and macrophages can attack tumor directly, and class II+ APC may help mark micro-tumor sites.