Considerations in the Diagnosis and Management of Pulmonary Hypertension Associated With Left Heart Disease.

Pulmonary hypertension associated with left heart disease (PH-LHD) remains the most common cause of pulmonary hypertension globally. Etiologies include heart failure with reduced and preserved ejection fraction and left-sided valvular heart diseases. Despite the increasing prevalence of PH-LHD, there remains a paucity of knowledge about the hemodynamic definition, diagnosis, treatment modalities, and prognosis among clinicians. Moreover, clinical trials have produced mixed results on the usefulness of pulmonary vasodilator therapies for PH-LHD. In this expert review, we have outlined the critical role of meticulous hemodynamic evaluation and provocative testing for cases of diagnostic uncertainty. Therapeutic strategies-pharmacologic, device-based, and surgical therapies used for managing PH-LHD-are also outlined. PH-LHD in advanced heart failure, and the role of mechanical circulatory support in PH-LHD is briefly explored. An in-depth understanding of PH-LHD by all clinicians is needed for improved recognition and outcomes among patients with PH-LHD.

Predictors and Impact of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation.

Background: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known. Objectives: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation. Methods: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m2 and systemic vascular resistance <800 dyne/s/cm5, and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed. Results: Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; P = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index. Conclusions: Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted.

Sex Disparities in Left Ventricular Assist Device Implantation: Delayed Presentation and Worse Right Heart Failure.

We explored whether women undergo continuous-flow left ventricular assist device (CF-LVAD) implantation in later stages of heart failure (HF) than men, evidenced by worse preoperative right HF (RHF). We also compared two propensity models with and without preoperative RHF to assess its effect on outcomes. INTERMACS was queried from July 2008 to December 2017. Propensity model 1 matched men and women on age ≥50 years, HF etiology, body surface area, INTERMACS class, comorbidities, device strategy, temporary mechanical circulatory support, and device type. Model 2 included these variables plus LV end-diastolic diameter, right atrial pressure/pulmonary capillary wedge pressure, pulmonary artery pulsatility index, and right ventricular ejection fraction. The primary outcome was all-cause mortality. Secondary outcomes comprise RHF, rehospitalization, renal dysfunction, stroke, and device malfunction. In model 1, characteristics were comparable between 3,195 women and 3,195 men, except women more often had preoperative RHF and postoperative right VAD support and had worse 1 year and overall survival. In model 2, after propensity matching for additional risk factors for preoperative RHF, 1,119 women and 1,119 men had comparable post-LVAD implant RVAD use and survival. These findings suggest that women present more often with biventricular failure and after implantation have higher RHF and mortality rates.

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.

Clinical Predictors and Outcomes After Left Ventricular Assist Device Implantation and Tracheostomy.

BACKGROUND: Postoperative respiratory failure is a major complication that affects up to 10% of patients who undergo cardiac surgery and has a high in-hospital mortality rate. Few studies have investigated whether patients who require tracheostomy for postoperative respiratory failure after continuous-flow left ventricular assist device (CF-LVAD) implantation have worse survival outcomes than patients who do not. OBJECTIVE: To identify risk factors for respiratory failure necessitating tracheostomy in CF-LVAD recipients and to compare survival outcomes between those who did and did not require tracheostomy. METHODS: Consecutive patients who underwent primary CF-LVAD placement at a single institution between August 1, 2002, and December 31, 2019, were retrospectively reviewed. Propensity score matching accounted for baseline differences between the tracheostomy and nontracheostomy groups. Multivariate logistic regression was used to identify tracheostomy risk factors and 90-day survival; Kaplan-Meier analysis was used to assess midterm survival. RESULTS: During the study period, 664 patients received a CF-LVAD; 106 (16.0%) underwent tracheostomy for respiratory failure. Propensity score matching produced 103 matched tracheostomy-nontracheostomy pairs. Patients who underwent tracheostomy were older (mean [SD] age, 57.9 [12.3] vs 54.6 [13.9] years; P = .02) and more likely to need preoperative mechanical circulatory support (61.3% vs 47.8%; P = .01) and preoperative intubation (27.4% vs 8.8%; P < .001); serum creatinine was higher in the tracheostomy group (mean [SD], 1.7 [1.0] vs 1.4 [0.6] mg/dL; P < .001), correlating with tracheostomy need (odds ratio, 1.76; 95% CI, 1.21-2.56; P = .003). Both before and after propensity matching, 30-day, 60-day, 90-day, and 1-year survival were worse in patients who underwent tracheostomy. Median follow-up was 0.8 years (range, 0.0-11.2 years). Three-year Kaplan-Meier survival was significantly worse for the tracheostomy group before (22.0% vs 61.0%; P < .001) and after (22.4% vs 48.3%; P < .001) matching. CONCLUSION: Given the substantially increased probability of death in patients who develop respiratory failure and need tracheostomy, those at high risk for respiratory failure should be carefully considered for CF-LVAD implantation. Comprehensive management to decrease respiratory failure before and after surgery is critical.

Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).

Broadening Heart Failure Care Beyond Cardiology: Challenges and Successes Within the Landscape of Multidisciplinary Heart Failure Care.

PURPOSE OF REVIEW: Heart failure (HF) is a growing public health concern that impairs the quality of life and is associated with significant mortality. As the prevalence of heart failure increases, multidisciplinary care is essential to provide comprehensive care to individuals. RECENT FINDINGS: The challenges of implementing an effective multidisciplinary care team can be daunting. Effective multidisciplinary care begins at the initial diagnosis of heart failure. The transition of care from the inpatient to the outpatient setting is critically important. The use of home visits, case management, and multidisciplinary clinics has been shown to decrease mortality and heart failure hospitalizations, and major society guidelines endorse multidisciplinary care for heart failure patients. Expanding heart failure care beyond cardiology entails incorporating primary care, advanced practice providers, and other disciplines. Patient education and self-management are fundamental to multidisciplinary care, as is a holistic approach to effectively address comorbid conditions. Ongoing challenges include navigating social disparities within heart failure care and limiting the economic burden of the disease.

Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions.

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation of the angiotensin system. ARNi therapy is very effective in reducing the risks of death and hospitalization for HF in patients with HF and New York Heart Association functional class II to III symptoms, but studies failed to show any benefits with ARNi when compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in patients with advanced HF with reduced ejection fraction or in patients following myocardial infarction with left ventricular dysfunction but without HF. These raise the questions about whether the enzymatic breakdown of natriuretic peptides may not be a very effective solution in advanced HF patients when there is downstream blunting of the response to natriuretic peptides or among post-myocardial infarction patients in the absence of HF when there may not be a need for increased natriuretic peptide availability. Furthermore, there is a need for additional studies to determine the long-term effects of ARNi on albuminuria, obesity, glycemic control and lipid profile, blood pressure, and cognitive function in patients with HF.

Continuous-Flow Ventricular Assist Device Support in Adult Congenital Heart Disease: A 15-Year, Multicenter Experience of Temporary and Durable Support.

Heart failure (HF) is common in adult congenital heart disease (ACHD) patients; however, use of continuous-flow ventricular assist devices (CF-VADs) remains rare. We reviewed outcomes of patients with congenital heart disease greater than or equal to 18 years of age at the time of CF-VAD implant at the affiliated pediatric and adult institutions between 2006 and 2020. In total, 18 ACHD patients (15 with great anatomical complexity) received 21 CF-VADs. Six patients (median age 34 years) received seven percutaneous CF-VADs with a median duration of support of 20 days (3-44 days) with all patients survived to hospital discharge and two patients were bridged to durable CF-VADs. Fourteen patients (median age 38 years) received durable CF-VADs. Thirteen patients (93%) survived to hospital discharge and the median duration of support was 25.8 months (6.4-52.1 months). Estimated survival on durable CF-VAD at 1, 3, and 5 years was 84%, 72%, and 36%, respectively. Three patients were successfully bridged to transplantation. Device-related complications include cerebrovascular accident (n = 5), driveline infection (n = 3), device infection requiring chronic antibiotic therapy (n = 4), gastrointestinal bleeding (n = 6), and presumed pump thrombosis (n = 5). These results show percutaneous and durable CF-VADs can support ACHD patients with advanced HF.

Impact of Cancer Care Regionalization on Patient Volume.

BACKGROUND: Cancer centers are regionalizing care to expand patient access, but the effects on patient volume are unknown. This study aimed to compare patient volumes before and after the establishment of head and neck regional care centers (HNRCCs). METHODS: This study analyzed 35,394 unique new patient visits at MD Anderson Cancer Center (MDACC) before and after the creation of HNRCCs. Univariate regression estimated the rate of increase in new patient appointments. Geospatial analysis evaluated patient origin and distribution. RESULTS: The mean new patients per year in 2006-2011 versus 2012-2017 was 2735 ± 156 patients versus 3155 ± 207 patients, including 464 ± 78 patients at HNRCCs, reflecting a 38.4 % increase in overall patient volumes. The rate of increase in new patient appointments did not differ significantly before and after HNRCCs (121.9 vs 95.8 patients/year; P = 0.519). The patients from counties near HNRCCs, showed a 210.8 % increase in appointments overall, 33.8 % of which were at an HNRCC. At the main campus exclusively, the shift in regional patients to HNRCCs coincided with a lower rate of increase in patients from the MDACC service area (33.7 vs. 11.0 patients/year; P = 0.035), but the trend was toward a greater increase in out-of-state patients (25.7 vs. 40.3 patients/year; P = 0.299). CONCLUSIONS: The creation of HNRCCs coincided with stable increases in new patient volume, and a sizeable minority of patients sought care at regional centers. Regional patients shifted to the HNRCCs, and out-of-state patient volume increased at the main campus, optimizing access for both local and out-of-state patients.

Impact of time off anticoagulation in patients with continuous-flow left ventricular assist devices.

Patients with left ventricular assist devices (LVADs) receive anticoagulation to decrease the risk of thrombosis. Various circumstances require discontinuing anticoagulation in LVAD patients, but the risks entailed are not well defined. In a retrospective review of LVAD implantation procedures, we examined the effect of time off anticoagulation on thrombosis and mortality rates after implantation. An international normalized ratio ≤ 1.5 was used to screen for patients taken off anticoagulation. Patients were divided into three groups by the cumulative number of days off anticoagulation: no discontinuation, short-term discontinuation (< 30 days), and long-term discontinuation (≥ 30 days). Rates of ischemic stroke, pump thrombosis, and mortality were compared among groups. Of 245 patients who underwent LVAD implantation during the study, 70 (28.6%) were off anticoagulation during follow-up: 37 (15.1%) had short-term discontinuation (median, 11 days), and 33 (13.5%) had long-term discontinuation (median, 124 days). Patients with long-term discontinuation had a higher rate of ischemic stroke (adjusted hazard ratio 8.5, p = 0.001) and death (adjusted hazard ratio 3.9, p = 0.001). The three groups did not differ in pump thrombosis rate. We conclude that after LVAD implantation, discontinuing anticoagulation for ≥ 30 days is independently associated with an increased risk of ischemic stroke and death.

Impact of sarcopenia on post-liver transplant morbidity and mortality in cirrhotic patients.

BACKGROUND: Modalities available for severity assessment and prediction of complications after liver transplant (LT) in cirrhotic patients are model for end-stage liver disease-sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores. The limitation of these scores is the lack of assessment of nutritional and functional status. Sarcopenia is a newer modality, which is developed for objective assessment of nutritional status. The aim of this study is to analyze the significance of sarcopenia in predicting 1-year mortality and morbidity in post-LT patients. METHODS: In this retrospective study, patients who underwent LT for cirrhosis between January 2013 and December 2018 were included. A computerized tomography (CT) image was used to analyze the psoas muscle index at the L3 vertebra (L3-PMI), and sarcopenia was defined as the values belonging to the lowest quartile of L3-PMI. The effect of sarcopenia on mortality and morbidity in terms of requirement for mechanical ventilation, duration of hospital stay, and occurrence of infections was studied. RESULTS: Among the study population (n = 74), 71 were men and the mean age was 51 years. Sarcopenia was observed in 27% (n = 20). Fifteen recipients had mortality within 1 year after transplant. In our analysis, sarcopenia was significantly associated with 1-year mortality (sensitivity 60%, specificity 81%; positive predictive value [PPV] 45%; negative predictive value [NPV] 88%; and p-value 0.001). Duration of mechanical ventilation, total hospital stay, and occurrence of infection were not significantly associated with sarcopenia. Sarcopenia was found as an independent predictor of mortality on binary logistic regression. CONCLUSION: The preoperative sarcopenia index in cirrhotic patients can predict the risk of mortality in post-liver transplant patients.

Unilateral Angiokeratoma of Fordyce With Unilateral PEAKER: A Rare Presentation of an Uncommon Disease.

Angiokeratomas are benign vascular lesions that can occur anywhere in the body. Fordyce angiokeratomas, also known as genital angiokeratomas, often develop on the vulva in women and the scrotum in males. A subtype of genital angiokeratoma in males is called penile angiokeratoma (PEAKER). In females, clitoral angiokeratoma (CLANKER) is the embryologic equivalent. As a result of the underlying pathophysiology, these lesions are often bilateral. Unilateral Fordyce angiokeratoma instances are infrequent, and unilateral PEAKER cases have never been previously documented. We describe a case of Fordyce's unilateral angiokeratoma with unilateral PEAKER. To the best of our knowledge, such a variation in presentation of this rare disease has not been previously reported.

Relation of T Wave Positivity in Lead aVR to Ischemic Etiology of Cardiomyopathy.

Identifying ischemic etiology of cardiomyopathy carries prognostic and therapeutic significance. Clinical and electrocardiographic parameters can predict ischemic cardiomyopathy. Positive T wave polarity in lead aVR (TPaVR) has been associated with adverse cardiac events and severity of coronary artery disease. Medical records of adults evaluated in an advanced heart failure referral clinic for cardiomyopathy with systolic dysfunction (ejection fraction ≤ 40%) were retrospectively reviewed. Patients with ventricular pacing were excluded. Significant predictors of ischemic cardiomyopathy from a univariate logistic regression model were entered simultaneously into a multivariate logistic regression model. A total of 180 patients met study inclusion criteria. Mean age of the population was 52.5 ± 15.3 years old and 65% were men. Ischemic cardiomyopathy was present in 52 patients (29%). Positive TPaVR was present in 57 patients (32%). Ischemic cardiomyopathy was more common in patients with positive TPaVR (63% vs 13%, p < 0.001). Ischemic cardiomyopathy was independently predicted by male gender, diabetes, hyperlipidemia, absence of family history of cardiomyopathy, echocardiographic regional wall motion abnormality, and positive TPaVR. The strongest association was with positive TPaVR (odds ratio 30.5, 95% confidence interval 6.47 to 214; p < 0.001). T wave amplitude of +0.025 mV in lead aVR was the optimal cutoff to distinguish ischemic and nonischemic cardiomyopathy in receiver operating characteristic analysis (sensitivity 69.2%, specificity 83.6%, area under curve = 0.747, 95% confidence interval 0.658 to 0.836). In conclusion, positive TPaVR was a strong predictor of ischemic etiology of cardiomyopathy.