Determinants of pulmonary hypertension in patients with end-stage kidney disease and arteriovenous access.

BACKGROUND: Pulmonary Hypertension (PH) is a sequela of arteriovenous (AV) fistulas (AVF) or AV grafts (AVG) in patients with end-stage kidney disease (ESKD) due to the creation of shunt physiology and increased pulmonary blood flow. PH has been consistently associated with increased mortality but there is a paucity of data regarding management. RESEARCH QUESTION: The objective of this study was to identify risk factors and outcomes in patients who develop PH after AVF or AVG creation for hemodialysis access. METHODS: Using the United States Renal Data System, we identified all patients over age 18 initiated on dialysis from 2012-2019 who did not receive renal transplant. We identified a) the predictors of PH in patients with ESKD on hemodialysis; b) the independent mortality risk associated with development of PH. RESULTS: We identified 478,896 patients initiated on dialysis from 2012-2019 of whom 27,787 (5.8 %) had a diagnosis of PH. The median age was 65 (IQR: 55-74) years and 59.1 % were male. Reduced ejection fraction, any congestive heart failure, obstructive sleep apnea, and female sex were the strongest predictors of PH diagnosis. Both AVG and AVF were also associated with an increased rate of PH diagnosis compared to catheter-based dialysis (p < 0.001). PH portended a poor prognosis and was associated with significantly increased mortality (p < 0.001). CONCLUSIONS: Patients with AVF or AVG should be screened using echocardiography prior to creation and monitored with serial echocardiography for the development of PH, and if present, considered for revision of the AVA. This is also the first study to identify that AVG are a risk factor for PH in dialysis patients.

Post-Capillary Pulmonary Hypertension: Clinical Review.

Pulmonary hypertension (PH) caused by left heart disease, also known as post-capillary PH, is the most common etiology of PH. Left heart disease due to systolic dysfunction or heart failure with preserved ejection fraction, valvular heart disease, and left atrial myopathy due to atrial fibrillation are causes of post-capillary PH. Elevated left-sided filling pressures cause pulmonary venous congestion due to backward transmission of pressures and post-capillary PH. In advanced left-sided heart disease or valvular heart disease, chronic uncontrolled venous congestion may lead to remodeling of the pulmonary arterial system, causing combined pre-capillary and post-capillary PH. The hemodynamic definition of post-capillary PH includes a mean pulmonary arterial pressure > 20 mmHg, pulmonary vascular resistance < 3 Wood units, and pulmonary capillary wedge pressure > 15 mmHg. Echocardiography is important in the identification and management of the underlying cause of post-capillary PH. Management of post-capillary PH is focused on the treatment of the underlying condition. Strategies are geared towards pharmacotherapy and guideline-directed medical therapy for heart failure, surgical or percutaneous management of valvular disorders, and control of modifiable risk factors and comorbid conditions. Referral to centers with advanced heart and pulmonary teams has shown to improve morbidity and mortality. There is emerging interest in the use of targeted agents classically used in pulmonary arterial hypertension, but current data remain limited and conflicting. This review aims to serve as a comprehensive summary of postcapillary PH and its etiologies, pathophysiology, diagnosis, and management, particularly as it pertains to advanced heart failure.

Combined Heart Kidney Transplantation Versus Heart Transplant in Patients with Renal Failure: Contemporary Insights and Future Perspectives.

PURPOSE OF REVIEW: In this review, we aim to outline the criteria regarding the evaluation of patients with chronic renal disease (CKD) awaiting heart transplantation and discuss the outcomes of combined heart/kidney transplantation. Herein, we also review pathophysiology and risk factors that predispose to chronic kidney disease (CKD) and acute kidney injury (AKI) in patients with HF and after OHT. RECENT FINDINGS: In patients with end-stage systolic heart failure (HF) and an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, orthotopic heart transplantation (OHT) alone is a relative contraindication, with a consensus that these patients are better served with heart-kidney transplant (HKT). However, there is significant variation between institutions regarding timing and indication for heart/kidney transplantation, with little data available to predict post-transplant outcomes. A Scientific Statement from American Heart Association was published detailing the indications, evaluation, and outcomes for Heart-Kidney Transplantation, and noted a steady rise in the incidence of heart/kidney dual organ transplants. Recently, the Organ Procurement and Transplantation Network (OPTN) Multi-Organ Transplantation Committee implemented a safety net policy for heart transplant recipients who do need meet criteria for simultaneous heart-kidney transplant in 2023 but with a likely need for sequential kidney transplantation. Optimization of organ distribution and patient outcomes after cardiac transplantation requires appropriate recipient selection. This review also outlines the criteria regarding the evaluation of patients with CKD awaiting heart transplantation and outcomes of combined HKT.

A multicenter evaluation of the HeartMate 3 risk score.

BACKGROUND: The Heartmate 3 (HM3) risk score (HM3RS) was derived and validated internally from within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial population and provides 1- and 2-year mortality risk prediction for patients in those before HM3 left ventricular assist device (LVAD) implantation. We aimed to evaluate the HM3RS in nontrial unselected patients, including those not meeting inclusion criteria for MOMENTUM 3 trial enrollment. METHODS: Patients who underwent HM3 LVAD implant at 1 of 7 US centers between 2017 and 2021, with at least 1-year follow-up, were included in this analysis. Patients were retrospectively assessed for their eligibility for the MOMENTUM 3 trial based on study inclusion and exclusion criteria. HM3RS risk discrimination was evaluated using time-dependent receiver operating characteristic curve analysis for 1-year mortality for all patients and further stratified by MOMENTUM 3 trial eligibility. Kaplan-Meier curves were constructed using the HM3RS-based risk categories. RESULTS: Of 521 patients included in the analysis, 266 (51.1%) would have met enrollment criteria for MOMENTUM 3. The 1- and 2-year survival for the total cohort was 85% and 81%, respectively. There was no statistically significant difference in survival between those who met and did not meet enrollment criteria at 1 (87% vs 83%; p = 0.21) and 2 years postimplant (80% vs 78%; p = 0.39). For the total cohort, HM3RS predicted 1-year survival with an area under the curve (AUC) of 0.63 (95% confidence interval [CI]: 0.57-0.69, p < 0.001). HM3RS performed better in the subset of patients meeting enrollment criteria: AUC 0.69 (95% CI:0.61-0.77, p < 0.001) compared to the subset that did not: AUC 0.58 (95% CI: 0.49-0.66, p = 0.078). CONCLUSIONS: In this real-world evidence, multicenter cohort, 1- and 2-year survival after commercial HM3 LVAD implant was excellent, regardless of trial eligibility. The HM3RS provided adequate risk discrimination in "trial-like" patients, but predictive value was reduced in patients who did not meet trial criteria.

Transcatheter Edge-to-Edge Repair for Tricuspid Regurgitation-A Systematic Review and Meta-Analysis.

Transcatheter edge-to-edge repair (TEER) has emerged as a widely accepted procedure for tricuspid regurgitation (TR) as gauged by echocardiographic parameters and clinical outcomes. Our study aims to assess TR severity and other echocardiographic outcomes in patients undergoing TEER with TriClip, MitraClip, and PASCAL devices. A literature search of 5 databases was performed until 1st June 2023. Randomized controlled trials (RCTs) or observational studies with moderate to severe (grade III-V) TR patients undergoing isolated TEER were considered eligible. Echocardiographic, and quality of life determining outcomes such as improvement in TR severity grade ≥3, New York Heart Association (NYHA) class ≥3, procedural success, 6-minute walking distance (6MWD), and adverse outcomes were analyzed. Grade assessment was performed and studies were assessed for risk of bias and publication bias. We included 15 studies (14 observational and 1 RCT) in our paper. Analysis revealed a substantial reduction in TR volume (P < 0.00001), TR grading (P < 0.00001), tricuspid annular diameter (P < 0.00001), proximal isovelocity surface area radius (P < 0.00001), effective regurgitant orifice area (P < 0.00001), and improvement in NYHA class (P < 0.00001) at 30 days from baseline, postprocedurally. A significant increase in 6MWD at 1 year (P = 0.001) was also recorded. No significant differences in left ventricular ejection fraction (P = 0.87), fractional area change (P = 0.37), or tricuspid annular plane systolic excursion (P = 0.76) were observed. TEER procedural success was 97%. TEER produced a significant reduction in TR grade and volume, NYHA class, 6MWD, and showed prominent procedural success. Large scale RCTs comparing the TEER devices are needed to strengthen the present findings.

Transcatheter Edge-to-Edge Repair in Patients With End-Stage Renal Disease on Dialysis: A USRDS Registry Study.

Transcatheter edge-to-edge repair (TEER) of the mitral valve has become standard of care for the treatment of high-risk patients with severe mitral regurgitation. Patients with end stage renal disease (ESRD) on hemodialysis were either excluded or severely underrepresented in all seminal trials proving the safety and efficacy of TEER. There have been few studies that evaluated the effectiveness or complications of TEER in ESRD patients. Using the United States Renal Data System (USRDS), we identified all ESRD patients who underwent TEER from October 2015 to December 31, 2019. Major comorbidities were recorded and Kaplan-Meier curves were generated for survival and freedom from hospitalization or death. The study population included 965 patients, of which 576 (59.7%) were male. The median age at the time of TEER was 72.5 (IQR: 64.4-79.1) years. There were 130 (13.2%) patients with heart failure with reduced ejection fraction (HFrEF), 110 (11.2%) with heart failure with preserved ejection fraction (HFpEF) and 745 (74.6%) with an indeterminate ejection fraction. During follow-up, strokes occurred in 61 (6.3%) patients, infective endocarditis in 42 (4.4%) patients, mitral stenosis in 13 (1.3%) and valve embolism in less than 11 patients. One-year survival was 56.9%, and 2-year survival was 33.9%. In patients with ESRD undergoing TEER, only a preserved ejection fraction (HR: 0.70, 95% CI: 0.50-0.99, P = 0.041) was a significant predictor of survival in a cox proportional hazards model. Despite favorable in-hospital outcomes one-year mortality rates surpass those reported in broader patient cohorts. The increased incidence of infective endocarditis and mitral stenosis is likely related to increased risk intrinsic to those with ESRD.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

The Value of Right Heart Catheterization: Case Series Showing Benefits in a Variety of Diagnoses.

Although the right heart catheterization (RHC) was first introduced in 1945, its use in the quantitative hemodynamic assessment of patients has remained of questionable benefit. With recent advances in pharmacotherapies and mechanical support devices, RHC has been increasingly used to assess and help tailor the management of more complex patient scenarios. We present a case series in which the use of the RHC was helpful in making complex medical decisions. (Level of Difficulty: Intermediate.).

Trends in cardiovascular complications of pregnancy: A nationwide inpatient sample analysis.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of pregnancy-related mortality in the United States. Physiologic stress of pregnancy can induce several hemodynamic changes that contribute to an increased risk of cardiac complications in the peripartum period. There are ongoing efforts to improve cardiovascular mortality in pregnant patients. Understanding trends in cardiovascular complications during pregnancy may provide insight into improving care for high-risk pregnancies. METHODS: We retrospectively analyzed data from the National Inpatient Sample (NIS) Database and identified all inpatient hospitalizations for pregnancy and delivery. We then analyzed trends in the rates of cardiac complications in the pregnant patient. RESULTS: There are concerning increases in trends of cardiac complications and comorbidities in pregnant people including: acute coronary syndrome, spontaneous coronary artery dissection, cardiogenic shock, pulmonary hypertension, chronic congestive heart failure, heart transplant, aortic syndromes, stroke, and pulmonary embolism. While the rates of STEMI have decreased, the incidence of peripartum cardiomyopathy has remained stable. CONCLUSION: There are concerning increases in certain cardiac complications during pregnancy. This is likely due to increasing age at the time of pregnancy and associated comorbidities.

Aortic Valve Replacement in Patients With ESRD and Heart Failure With Reduced Ejection Fraction.

Transcatheter aortic valve replacement (TAVR) has become the standard of care for the treatment of all patients with calcific aortic stenosis. Patients with end-stage renal disease (ESRD) on hemodialysis were excluded from participation in many of the seminal trials proving the safety and efficacy of TAVR. The outcomes of TAVR in the ESRD population from a national registry showed significantly higher in-hospital and 1-year mortality compared with patients not on hemodialysis. Comparisons of outcomes for surgical versus transcatheter interventions in patients with ESRD and heart failure with reduced ejection fraction (HFrEF) are limited. Using the United States Renal Data System, we identified all ESRD patients with aortic stenosis and HFrEF who underwent TAVR, surgical aortic valve replacement (SAVR), or those with HFrEF and aortic stenosis initiated on dialysis after the year 2012 to compare survival. Propensity score matching was performed, and groups were compared using Kaplan-Meier curves. The study population consisted of 7,660 patients, of which 5,064 (66.1%) were male. The median age at initiation of dialysis was 73 years (interquartile range: 65 to 80). There were 1,108 (14.5%) who underwent TAVR and 695 (9.1%) who underwent SAVR. After matching, patients who underwent TAVR had increased survival relative to those who were medically managed. In-hospital outcomes favored TAVR with less mortality and fewer complications when compared with SAVR. TAVR had improved mortality relative to SAVR in the early period, but survival curves crossed at approximately 9 months and SAVR had better mortality in the long-term. TAVR is a safe and effective procedure and is associated with improved mortality when compared with medical management. In conclusion, TAVR and SAVR are both viable options for patients with ESRD and HF with TAVR having better short-term outcomes and SAVR better long-term outcomes.

Natriuretic peptide biomarkers in the imminent development of preeclampsia.

Preeclampsia is the most common cause of morbidity and mortality in pregnancy, the incidence being significantly higher in low-income countries with reduced access to health care. Women with preeclampsia are at a higher risk of developing cardiovascular disease with a poorer long-term outcome. Early recognition and treatment are key to improving short- and long-term outcomes. Approximately 3%-5% of pregnant women will develop preeclampsia, with potentially fatal outcomes. Despite ongoing research, the exact pathophysiologic mechanism behind its development remains unclear. In this brief report, we describe the potential role of natriuretic peptides as biomarkers in the imminent development of preeclampsia. In a retrospective manner, we analyzed changes in the left ventricular ejection fraction and left atrial volume and increases in natriuretic peptide in correlation with the development of preeclampsia. We found that three out of four patients developed a significant increase in natriuretic peptide, which correlated with the development of preeclampsia and/or peripartum cardiomyopathy. Significant increases in natriuretic peptides around the time of delivery might be a marker for the imminent development of preeclampsia. Close monitoring of natriuretic peptide levels in the peripartum period could give important insight into the imminent development of preeclampsia in high-risk patients. Close follow-up in specialized cardio-obstetric clinics is highly recommended.

Catheter-Directed Thrombolysis or Catheter-Based Thrombectomy in Acute Pulmonary Embolism: Horses for Courses.

Venous thromboembolism is a common disorder encompassing both pulmonary embolism (PE) and deep vein thrombosis (DVT). In the United States, up to 2 million people are diagnosed with DVT and 600,000 with PE annually. The purpose of this review is to discuss the indications and evidence for catheter-directed thrombolysis versus catheter-based thrombectomy.

Cardiopulmonary Exercise Testing, Rehabilitation, and Exercise Training in Postpulmonary Embolism.

Long-term exercise intolerance and functional limitations are common after an episode of acute pulmonary embolism (PE), despite 3 to 6 months of anticoagulation. These persistent symptoms are reported in more than half of the patients with acute PE and are referred as "post-PE syndrome." Although these functional limitations can occur from persistent pulmonary vascular occlusion or pulmonary vascular remodeling, significant deconditioning can be a major contributing factor. Herein, the authors review the role of exercise testing to elucidate the mechanisms of exercise limitations to guide next steps in management and exercise training for musculoskeletal deconditioning.

Late Right Heart Failure After Left Ventricular Assist Device Implantation: Contemporary Insights and Future Perspectives.

Late right heart failure (RHF) is increasingly recognized in patients with long-term left ventricular assist device (LVAD) support and is associated with decreased survival and increased incidence of adverse events such as gastrointestinal bleeding and stroke. Progression of right ventricular (RV) dysfunction to clinical syndrome of late RHF in patients supported with LVAD is dependent on the severity of pre-existing RV dysfunction, persistent or worsening left- or right-sided valvular heart disease, pulmonary hypertension, inadequate or excessive left ventricular unloading, and/or progression of the underlying cardiac disease. RHF likely represents a continuum of risk with early presentation and progression to late RHF. However, de novo RHF develops in a subset of patients leading to increased diuretic requirement, arrhythmias, renal and hepatic dysfunction, and heart failure hospitalizations. The distinction between isolated late RHF and RHF due to left-sided contributions is lacking in registry studies and should be the focus of future registry data collection. Potential management strategies include optimization of RV preload and afterload, neurohormonal blockade, LVAD speed optimization, and treatment of concomitant valvular disease. In this review, the authors discuss definition, pathophysiology, prevention, and management of late RHF.

Transcatheter Aortic Valve Implantation in Cardiac Amyloidosis and Aortic Stenosis.

Aortic stenosis (AS) and cardiac amyloidosis (CA) occur concomitantly in a significant number of patients and portend a higher risk of all-cause mortality. Previous studies have investigated outcomes in patients with concomitant CA/AS who underwent transcatheter aortic valve implantation (TAVI) versus medical therapy alone, but no evidence-based consensus regarding the ideal management of these patients has been established. Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Methodologic bias was assessed using the modified Newcastle-Ottawa scale for observational studies. A total of 4 observational studies comprising 83 patients were included. Of these, 45 patients (54%) underwent TAVI, whereas 38 (46%) were managed conservatively. Of the 3 studies that included baseline characteristics by treatment group, 30% were women. The risk of all-cause mortality was found to be significantly lower in patients who underwent TAVI than those treated with conservative medical therapy alone (odds ratio 0.24, 95% confidence interval 0.08 to 0.73). In conclusion, this meta-analysis suggests a lower risk of all-cause mortality in patients with CA with AS who underwent TAVI than those managed with medical therapy alone.