Pulmonary hypertension secondary to valvular heart disease: a state-of-the-art review.

Pulmonary hypertension (PH) is a common disease affecting up to 1% of the population and at least 50% of patients diagnosed with heart failure (HF) (Hoeper et al. in Lancet Respir Med 4(4):306-322, 2016). It is estimated that PH is present in 15% to 60% of patients with valvular heart disease (VHD) which can result from an increase in pulmonary blood flow and subsequently in pulmonary venous congestion and pulmonary vascular resistance (PVR). It is important to identify the severity of PH in patients with VHD to appropriately risk stratify and manage these patients (Magne et al. in JACC Cardiovasc Imaging 8(1):83-99, 2015). In this review, we examine the diagnostic criteria for PH and its pathophysiology. We also focus on the growing evidence supporting the presence of PH secondary to VHD and describe the contemporary surgical and medical therapeutic interventions in this patient population (Fig. 1).

Conversion to tacrolimus alone compared to full immunosuppression following cardiac transplantation (TACTFUL).

BACKGROUND: Cardiac transplantation requires lifelong immunosuppressant medications to prevent rejection. However, some patients may not tolerate multiple immunosuppressants due to adverse effects. At our institution, patients may be converted to monotherapy with tacrolimus if unable to tolerate a combination regimen. This study evaluated the outcomes among patients converted to tacrolimus monotherapy compared with those maintained on combination immunosuppression. METHODS: This single-center, retrospective cohort study included patients who received heart transplants at Sentara Norfolk General Hospital between January 2015 and July 2021. Patients were classified as receiving tacrolimus monotherapy (Mono) or combination immunosuppression (Combo). The primary outcome was all-cause mortality with key secondary outcomes including incidence of 2R/3R rejection, necessity for renal replacement therapy, and infection. RESULTS: 112 patients were included (Mono = 25, Combo = 87). Median age at transplant was 53.8 years (Mono) and 52.1 years (Combo). The most common reasons for conversion to monotherapy were leukopenia, infection, and gastrointestinal (GI) distress. There was no difference in mortality (0 in Mono, 11 in Combo; p = .09) or percentage of patients with 2R/3R rejection (24% in Mono, 32.2% in Combo; p = .43). No Mono group patients experienced rejection after converting from combination therapy. 24% of Mono group patients resumed at least one additional immunosuppressive medication during the study period. Median time to monotherapy was 9.0 months, with a total median duration on monotherapy of 16.0 months. A median of 3.3 years of follow-up was observed for patients in Mono and 3.4 years in Combo (p = .29). CONCLUSION: Selected patients who do not tolerate combination immunosuppression can be safely transitioned to tacrolimus monotherapy as a means of controlling adverse events without an increased risk of mortality or rejection.

Challenges and the innovations in the care of advanced heart failure patients during COVID-19.

The COVID-19 pandemic underscored our healthcare system's unpreparedness to manage an unprecedented pandemic. Heart failure (HF) physicians from 14 different academic and private practice centers share their systems' challenges and innovations to care for patients with HF, heart transplantation, and patients on LVAD support during the COVID-19 pandemic. We discuss measures implemented to alleviate the fear in seeking care, ensure continued optimization of guideline directed medical therapy (GDMT), manage the heart transplant waiting list, continue essential outpatient monitoring of anticoagulation in LVAD patients and surveillance testing post-heart transplant, and prevent physician burnout. This collaborative work can build a foundation for better preparation in the face of future challenges.

The utilization and safety of apixaban for therapeutic anticoagulation in heart transplant population requiring routine endomyocardial biopsies.

PURPOSE: Routine endomyocardial (EM) biopsies pose a challenge in the management of heart transplant recipients requiring anticoagulation. Apixaban is a direct-acting oral anticoagulant (DOAC) with a short half-life allowing for brief interruptions of anticoagulation for procedures. The study objective was to determine the safety and efficacy of apixaban in heart transplant patients undergoing EM biopsies. METHODS: This retrospective case series evaluated patients with a heart transplant from April 1, 2017 to July 30, 2020 who were treated with apixaban within 90 days post-transplant. The primary outcome was the occurrence of a bleeding or thrombotic event. RESULTS: A total of 12 patients with >100 biopsies were included. The median age was 54 years (IQR 37-59) with a mean weight of 91 ± 20 kg. There were no bleeding or thrombotic events. During therapy, patients underwent an average of eight biopsies. The median time from transplant to initiation of apixaban was 39.5 days (range 9-77). Therapy was maintained without any need for reversal for a median of 276 days (IQR 45-245). CONCLUSIONS: Apixaban is safe to use for anticoagulation of heart transplant recipients undergoing routine biopsies. Using apixaban allows for a short interruption of therapeutic anticoagulation to accommodate a biopsy without increased risk of bleeding.

Procedural, clinical, and health status outcomes in chronic total coronary occlusion revascularization: Results from the PERSPECTIVE study.

BACKGROUND: Limited research has detailed the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) with independent core laboratory and event adjudication. This study examined procedural, clinical, and patient-reported health status outcomes among patients undergoing CTO PCI with specific focus on outcomes for those treated with zotarolimus-eluting stents (ZES). METHODS: Among 500 consecutive patients undergoing attempted CTO PCI, procedural and in-hospital clinical outcomes were examined in addition to the 1-year composite endpoint of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events, MACE). In a pre-specified cohort of 250 patients, health status measures were ascertained at baseline and 1 year. A powered secondary endpoint was 1-year MACE among patients treated with ZES compared with a performance goal. RESULTS: Demographic, lesion, and procedural characteristics for the overall population included prior bypass surgery, 29.8%; diabetes, 35.2%; occlusion length >20 mm, 71.3%; J-CTO score, 2.5 ± 1.1; and primary retrograde strategy, 30.8%. Overall guidewire crossing was 90.9%; clinical success following guidewire crossing, 94.3%; and 1-year MACE rate, 12.1%. One-year health status significantly improved from baseline with successful CTO-PCI (angina frequency, 72.7 ± 26.5 at baseline to 96.0 ± 10.8, p < .0001). Compared with a performance goal derived from prior CTO DES trials (1-year hierarchal MACE, 25.2%), treatment with ZES was associated with significantly lower MACE (18.2%, one-sided upper CI, 23.6%, p = .017). CONCLUSIONS: Favorable procedural success, health status improvements and late-term clinical outcomes inform the relative risks and benefits of CTO PCI when performed in a clinically indicated, complex patient population representative of those treated in clinical practice.

Practical guidance on the use of sacubitril/valsartan for heart failure.

Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that has been recommended in clinical practice guidelines to reduce morbidity and mortality in patients with chronic, symptomatic heart failure (HF) with reduced ejection fraction (HFrEF). This review provides an overview of ARNI therapy, proposes strategies to improve the implementation of sacubitril/valsartan in clinical practice, and provides clinicians with evidence-based, practical guidance on the use of sacubitril/valsartan in patients with HFrEF. Despite evidence demonstrating the benefits of ARNI therapy over standard of care, only a fraction of eligible patients takes sacubitril/valsartan. Barriers preventing the prescription of sacubitril/valsartan in eligible patients may include practitioners' unfamiliarity with ARNIs, safety concerns, and payer reimbursement issues. The optimal implementation of sacubitril/valsartan in clinical practice has the potential to reduce the overall burden of HF. Throughout this review, we describe our experience with sacubitril/valsartan, including strategies for the management of adverse events and common patient concerns. In addition, a strategy for the gradual introduction of sacubitril/valsartan using a treatment sequence scheme is proposed.

Updates on Device-Based Therapies for Patients with Heart Failure.

PURPOSE OF REVIEW: Heart failure is a growing epidemic. Optimal medical therapy remains the cornerstone of heart failure management but device-based therapies have been shown to contribute to morbidity and mortality reduction. RECENT FINDINGS: Multiple investigational trials had been conducted in the past decade that helped us better understand and manage heart failure. In this manuscript, we will discuss the major device related trials of year 2017 in the fields of defibrillators, hemodynamic monitoring, remote monitoring, autonomic nervous system modulation, ventricular assist devices, and device-based valvular heart disease management. Further research and trials in device-based therapies are needed to explore their long-term reduction in mortality and morbidity along with cost-effectiveness analyses in patients living with heart failure.

Update on obesity, the obesity paradox, and obesity management in heart failure.

Obesity is a major public health challenge worldwide. It is costly, predisposes to many cardiovascular (CV) diseases (CVD), is increasing at an alarming rate, and disproportionately affects people of low-socioeconomic status. It has a myriad of deleterious effects on the body, particularly on the CV system. Obesity is a major risk factor for heart failure (HF) and highly prevalent in this population, particularly in those with HF with preserved ejection fraction (HFpEF), to the extent that an obesity HFpEF phenotype has been proposed in the literature. However, once HF is developed, an obesity paradox exists where those with obesity have better short- and mid-term survival than normal or underweight individuals, despite a greater risk for hospitalizations. It may be argued that excess energy reserve, younger patient population, higher tolerability of HF therapy and better nutritional status may account for at least part of the obesity paradox on survival. Furthermore, body mass index (BMI) may not be an accurate measure of body composition, especially in HF, where there is an excess volume status. BMI also fails to delineate fat-free mass and its components, which is a better predictor of functional capacity and cardiorespiratory fitness (CRF), which particularly is increasingly being recognized as a risk modifier in both healthy individuals and in persons with comorbidities, particularly in HF. Notably, when CRF is accounted for, the obesity paradox disappears, suggesting that improving CRF might represent a therapeutic target with greater importance than changes in body weight in the setting of HF. In this narrative review, we discuss the current trends in obesity, the causal link between obesity and HF, an update on the obesity paradox, and a description of the major flaws of BMI in this population. We also present an overview of the latest in HF therapy, weight loss, CRF, and the application of these therapeutic approaches in patients with HF and concomitant obesity.

Clinical outcomes of ventricular assist device support by HIV infection status: An STS-INTERMACS analysis.

BACKGROUND: Cardiovascular disease remains the leading cause of mortality in human immunodeficiency virus-infected (HIV-positive) patients. Ventricular assist device therapy is rarely offered to these patients and data on outcomes are sparse. We investigated outcomes following ventricular assist device implants for HIV-positive as compared to non-HIV-infected (HIV-negative) patients. METHODS: We analyzed 22,065 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry for outcomes by HIV status. A propensity-matched analysis adjusting for 21 preimplant risk factors was also conducted. RESULTS: Compared with 21,980 HIV-negative device recipients, the 85 HIV-positive recipients were younger (median age 58 years vs 59 years, p = 0.02), had lower body mass index (26 kg/m2 vs 29 kg/m2, p = 0.001), and had higher rates of prior stroke (8% vs 4%, p = 0.02). In the matched HIV-positive and HIV-negative cohorts, there was significantly higher mortality in HIV-positive patients in earlier implant years, however, this association was not seen in later implant years (2018-2020). In both unmatched and matched cohorts, no significant differences in postimplantation stroke, major bleeding, or major infection were noted. CONCLUSIONS: With recent advancements in mechanical circulatory support and HIV treatment, ventricular assist device therapy is a viable therapeutic option for HIV-positive patients with end-stage heart failure.

Protocol-based anticoagulation management for mechanical circulatory support patients can be safe and efficient.

BACKGROUND: Achieving optimal anticoagulation remains a significant challenge in managing patients on left ventricular assist device (LVAD) support. Maintaining tight control of anticoagulation can be time-consuming but essential in preventing serious complications such as pump thrombosis and bleeding. OBJECTIVES: The efficacy and safety of a nurse coordinator-driven outpatient protocol (NCDOP) was evaluated for managing anticoagulation for LVAD patients. METHODS: A retrospective analysis was performed as part of a single-center quality improvement project. The primary outcome was time in therapeutic range (TTR), a measure of anticoagulation target efficacy before and after the implementation of the protocol. RESULTS: Among 47 patients, who served as their own control, there was no significant change in TTR or proportion of hospitalizations following institution of the protocol. Pre-NCDOP, there were six major bleeding and two thrombotic events, and none during the post-NCDOP period. CONCLUSIONS: A NCDOP is a reliable method to manage anticoagulation in LVAD patients and facilitates efficient care delivery. Future multicenter studies with larger patient cohorts are warranted to expand on the findings outlined in this manuscript.

Gastrointestinal Bleeding Rates in Left Ventricular Assist Device Population Reduced with Octreotide Utilization.

Patients with continuous-flow left ventricular assist devices have a high risk of gastrointestinal bleeding (GIB) and recurrent bleeding. Studies have shown octreotide can reduce the risk of GIB. This retrospective, case-crossover study, evaluated the efficacy of octreotide for the prevention of recurrent GIB in patients with left ventricular assist devices between August 2008 and October 2018. A total of 32 patients received octreotide and were included in the study. Hospital admission for GIB was evaluated before and after the initiation of octreotide. Each case served as his/her own control. Most patients were on a reduced aspirin dose (56.2%) and had a reduced international normalized ratio goal (59.4%) before starting monthly octreotide. The most common dose of long-acting octreotide was 30 mg every 28 days. Overall, octreotide decreased the frequency of GIB (4.3 vs. 0.9 events/year, p < 0.001). Nineteen (59.4%) patients did not have a subsequent gastrointestinal bleed. Of the 13 patients who rebled after initiation of octreotide, the frequency of events decreased by 2.6 bleeds per patient per year (4.8 vs. 2.2; p = 0.043). In high-risk patients who have failed conventional therapy, octreotide can be useful for the prevention of recurrent GIB.

Intoxicated Donors and Heart Transplant Outcomes: Long-Term Safety.

BACKGROUND: The opioid crisis has led to an increase in available donor hearts, although questions remain about the long-term outcomes associated with the use of these organs. Prior studies have relied on historical information without examining the toxicology results at the time of organ offer. The objectives of this study were to examine the long-term survival of heart transplants in the recent era, stratified by results of toxicological testing at the time of organ offer as well as comparing the toxicology at the time of donation with variables based on reported history. METHODS: The United Network for Organ Sharing database was requested as well as the donor toxicology field. Between 2007 and 2017, 23 748 adult heart transplants were performed. United Network for Organ Sharing historical variables formed a United Network for Organ Sharing Toxicology Score and the measured toxicology results formed a Measured Toxicology Score. Survival was examined by the United Network for Organ Sharing Toxicology Score and Measured Toxicology Score, as well as Cox proportional hazards models incorporating a variety of risk factors. RESULTS: The number and percent of donors with drug use has significantly increased over the study period (P<0.0001). Cox proportional hazards modeling of survival including toxicological and historical data did not demonstrate differences in post-transplant mortality. Combinations of drugs identified by toxicology were not associated with differences in survival. Lower donor age and ischemic time were significantly positively associated with survival (P<0.0001). CONCLUSIONS: Among donors accepted for transplantation, neither history nor toxicological evidence of drug use was associated with significant differences in survival. Increasing use of such donors may help alleviate the chronic donor shortage.

Short-term results with transcatheter aortic valve replacement for treatment of left ventricular assist device patients with symptomatic aortic insufficiency.

BACKGROUND: After 3 years of continuous-flow left ventricular assist device (CF-LVAD) support, nearly a third of patients develop at least moderate aortic insufficiency (AI). Percutaneous occluder devices, surgical aortic valve replacement (SAVR), and urgent heart transplantation are available treatment options. Transcatheter aortic valve replacement (TAVR) has not been widely used for treating symptomatic AI in patients on LVAD support. METHODS: Retrospective chart review and data analysis from October 2010 through August 2017 was performed. A total of 286 patients with end-stage heart failure (ESHF) were implanted with a durable CF-LVAD. Nine patients subsequently developed significant symptomatic AI, which was treated with TAVR. RESULTS: All 9 patients had 1 TAVR procedure with resolution of AI and were discharged home. Procedural complications include valve migration warranting a second valve for stabilization, retroperitoneal and groin hematoma, and pseudoaneurysm requiring thrombin injection. A significant improvement of the New York Heart Association classification was noted from the time of implant to 6 months. Two patients had unplanned heart failure‒related hospitalizations within 6 months. At 6 months, 89% of patients were alive on LVAD support. CONCLUSIONS: TAVR is a successful treatment modality for LVAD patients who develop symptomatic AI.