Early trends in cardiac allograft vasculopathy after implementation of the 2018 donor heart allocation policy in the United States.

STUDY OBJECTIVE: To evaluate the impact of the new donor heart allocation system implemented in the United States in October 2018 on development of early cardiac allograft vasculopathy (CAV). DESIGN: Retrospective cohort study. PARTICIPANTS: Adult (≥ 18 years) heart transplant recipients registered in the United Network for Organ Sharing database between October 18, 2015 and October 17, 2018 (old system) and October 18, 2018 and May 31, 2020 (new system). MAIN OUTCOME MEASURE: Incidence of angiographic CAV at 1 year (accelerated CAV) in the overall transplant population and among the highest acuity subgroup-Status 1A (old) and Status 1 or 2 (new). We included recipient and donor demographic, cardiovascular, and transplant factors in multivariable logistic regression models to identify predictors of accelerated CAV. RESULTS: Of 10,375 transplant recipients, 6,660 (64%) and 3,715 (36%) were listed in the old and new allocation cohorts, respectively. The incidence of accelerated CAV was 521 (8%) in the old period compared with 272 (7%) in the new period (P = .36). Similar incidence rates were observed in the highest acuity subgroup-363 (8%) compared with 143 (7%), respectively (P = .13). In adjusted analyses of the high-acuity cohort, the new allocation system was not associated with a higher likelihood of accelerated CAV (odds ratio = 0.87, 95% confidence interval: 0.70-1.08, P = .20). CONCLUSIONS: The new donor heart allocation system is not associated with development of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.

Aortic Pulsatility Index: A Novel Hemodynamic Variable for Evaluation of Decompensated Heart Failure.

BACKGROUND: Right heart catheterization for invasive hemodynamics has shown only modest correlation with clinical outcomes. We designed a novel hemodynamic variable that incorporates ventricular output and filling pressure. We anticipated that the aortic pulsatility index (API) would correlate with clinical outcomes in patients with heart failure. METHODS AND RESULTS: We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (February 2013 to November 2019). The API was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. The primary outcome was freedom from advanced therapies, defined as the need for inotropes, temporary mechanical circulatory support, a left ventricular assist device, or orthotopic heart transplantation, or death at 30 days. A total of 224 patient encounters, age 57 years (48-66 years; 34% women; 31% ischemic cardiomyopathy) were included. In univariable analysis, lower baseline API was significantly associated with progression to advanced therapies or death at 30-days (odds ratio 0.43, 95% confidence interval 0.30-0.61; P < .001) compared with those on continued medical management. Receiver operator characteristic analysis specified an optimal cutpoint of 1.45 for API. A Kaplan-Meier analysis indicated an association of API with the primary outcome (79% for API ≥ 1.45 vs 48% for API < 1.45). In multivariable analysis, higher API was strongly associated with freedom from advanced therapies or death (odds ratio 0.38, 95% confidence interval 0.22-0.65, P ≤ .001), even when adjusted for baseline characteristics and routine right heart catheterization measurements. CONCLUSIONS: The API is a novel invasive hemodynamic measurement that is associated independently with freedom from advanced therapies or death at 30-day follow-up.

Integrating Biomarkers and Imaging for Cardiovascular Disease Risk Assessment in Diabetes.

Cardiovascular disease (CVD) risk assessment has changed substantially in recent years. While older guidelines considered diabetes a coronary disease risk equivalent, more recent guidelines recommend risk stratification on the basis of global risk scoring to target intensity of therapy. While patients with diabetes as a whole are at greater risk for CVD events, these patients may also benefit from risk stratification based on circulating biomarkers like high-sensitivity C-reactive protein, high-sensitivity cardiac troponin T, and N-terminal pro-B-type natriuretic peptide, as well as newer imaging modalities (coronary artery calcium, carotid intima-media thickness, and myocardial perfusion imaging). The addition of these CVD risk assessment modalities could play an important role for deciding how aggressive a physician should be with pharmacological therapy. Here, we discuss many of the current recommendations of CVD risk assessment in patients with diabetes including newer modalities for CVD risk assessment.

Variations of coronary hemodynamic responses to intravenous adenosine infusion: implications for fractional flow reserve measurements.

BACKGROUND: Continuous intravenous adenosine infusion reportedly produces stable and maximal hyperemia to allow for fractional flow reserve (FFR) measurement; however, several observers have noted variation of the coronary/aortic (Pd/Pa) pressure ratio during the course of an adenosine infusion. METHODS: Pd/Pa pressure recordings during continuous peripheral intravenous adenosine infusion were examined in 51 patients (68 measurements) with data collected for at least 150 sec and for at least 30 sec after the lowest Pd/Pa reading. The lowest recorded Pd/Pa ratio was used as the true FFR value at maximal hyperemia. The highest subsequent Pd/Pa during the remaining period of adenosine infusion was recorded. A separate cohort of 12 patients had Pd/Pa values measured with both peripheral and central infusion. RESULTS: The average FFR value was 0.82 ± 0.10 and was recorded 99 ± 33 sec into the infusion. The Pd/Pa value showed a subsequent average increase of 0.08 ± 0.07 at 135 ± 32 sec. From the lowest measurement, Pd/Pa changed from a ratio ≤0.80 to >0.80 in 28% of recordings. In the cohort with matched recordings, central infusion reduced the severity (mean change of 0.08 vs. 0.11, P = 0.09) but not the incidence of Pd/Pa variability compared with peripheral infusion. CONCLUSION: Instability of Pd/Pa measurements is common over the course of a continuous intravenous adenosine infusion. FFR remains valid as the lowest value of Pd/Pa observed, however, Pd/Pa variability may subsequently occur and complicate pullback measurements for serial or multiple lesions.

Comparison of Cardiac Allograft Vasculopathy Incidence Between Simultaneous Multi-Organ and Isolated Heart Transplant Recipients in the United States.

BACKGROUND: Prior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multi-organ transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multi-organ heart transplants in the contemporary era. METHODS: We utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary endpoint was the development of angiographic CAV within 5 years of follow-up. RESULTS: Among 20,591 patients included in the analysis, 1,279 (6%) underwent multi-organ heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ) and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years and 74% were male. There were no significant between-group differences in cold ischemic time between the groups. The incidence of acute rejection during the first year after transplant was significantly lower in the multi-organ group (18% vs. 33%, p<0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multi-organ group (p<0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multi-organ heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio=0.76, 95% confidence interval: 0.66-0.88, p<0.01). CONCLUSIONS: Simultaneous multi-organ heart transplantation is associated with significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era.

Is Coronary Physiology Assessment Valid in Special Circumstances?: Aortic Stenosis, Atrial Fibrillation, Left Ventricular Hypertrophy, and Other.

Fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs) provide an important clinical tool to evaluate the hemodynamic significance of coronary lesions. However, these indices have major limitations. As these indices are meant to be surrogates of coronary flow, clinical scenarios such as aortic stenosis (with increased end-systolic and end-diastolic pressures) or atrial fibrillation (with significant beat-to-beat cardiac output variability) can have significant effect on the accuracy and reliability of these hemodynamic indices. Here, we provide a comprehensive evaluation of the pitfalls, limitations, and strengths of FFR and NHPRs in common clinical scenarios paired with coronary artery disease.

Impact of Age and Variant Time Period on Clinical Presentation and Outcomes of Hospitalized Coronavirus Disease 2019 Patients.

Objective: To evaluate the impact of age and COVID-19 variant time period on morbidity and mortality among those hospitalized with COVID-19. Patients and Methods: Patients from the American Heart Association's Get With The Guidelines COVID-19 cardiovascular disease registry (January 20, 2020-February 14, 2022) were divided into groups based on whether they presented during periods of wild type/alpha, delta, or omicron predominance. They were further subdivided by age (young: 18-40 years; older: more than 40 years), and characteristics and outcomes were compared. Results: The cohort consisted of 45,421 hospitalized COVID-19 patients (wild type/alpha period: 41,426, delta period: 3349, and omicron period: 646). Among young patients (18-40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.6; 95% CI, 1.3-2.1), major adverse cardiovascular events (MACE) (OR, 1.8; 95% CI, 1.3-2.5), and in-hospital mortality (OR, 2.2; 95% CI, 1.5-3.3) when compared with presentation during wild type/alpha. Among older patients (more than 40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.2; 95% CI, 1.1-1.3), MACE (OR, 1.5; 95% CI, 1.4-1.7), and in-hospital mortality (OR, 1.4; 95% CI, 1.3-1.6) when compared with wild type/alpha. Among older patients (more than 40 years), presentation during omicron associated with decreased odds of severe COVID-19 (OR, 0.7; 95% CI, 0.5-0.9) and in-hospital mortality (OR, 0.6; 95% CI, 0.5-0.9) when compared with wild type/alpha. Conclusion: Among hospitalized adults with COVID-19, presentation during a time of delta predominance was associated with increased odds of severe COVID-19, MACE, and in-hospital mortality compared with presentation during wild type/alpha. Among older patients (aged more than 40 years), presentation during omicron was associated with decreased odds of severe COVID-19 and in-hospital mortality compared with wild type/alpha.

Management of Coronary Complications.

Coronary complications are increasingly rare but remain fatal if not managed promptly and effectively. We review the incidence, management, and prevention of the most serious coronary complications including acute vessel closure from dissection, no-reflow, thrombosis, and air embolism as well as mechanical complications including perforation, stent dislodgment, and atherectomy burr entrapment.

Radial Hemostasis Is Facilitated With a Potassium Ferrate Hemostatic Patch: The STAT2 Trial.

OBJECTIVES: The aim of this trial was to test whether the potassium ferrate hemostatic patch (PFHP) as an adjunct to the TR Band (TRB) facilitated an early deflation protocol. BACKGROUND: Shorter TRB compression times may reduce the rate of radial artery occlusion (RAO) and reduce observation time after transradial access. METHODS: A total of 443 patients were randomized to the TRB or PFHP + TRB, with complete TRB deflation attempted 60 minutes postprocedure. The primary outcome was the time to successful full deflation of the TRB without bleeding, with secondary outcomes of time to discharge and complications including hematoma, RAO, or bleeding requiring intervention beyond TRB reinflation. RESULTS: Time to complete TRB deflation was 66 ± 14 minutes with the PFHP vs 113 ± 56 minutes for the TRB alone (P < 0.001). Minor rebleeding requiring TRB reinflation was much more frequent without the PFHP (0% vs 67.7%; P < 0.001) with 2.3 ± 1.3 additional reinflation and deflation attempts needed for hemostasis. Hematomas developed in 4.0% of the PFHP group and 6.8% of the TRB group (P = 0.20). RAO was rare (<1%), although 41% of patients received <5,000 U heparin. Among percutaneous coronary intervention patients, time to TRB deflation (68 ± 15 minutes vs 138 ± 62 minutes; P < 0.001) and composite complications (10.0% vs 24.2%; P = 0.04) were reduced with the PFHP. CONCLUSIONS: Compared with the TRB alone, the PFHP facilitated early 60-minute TRB deflation following transradial catheterization, with a numeric reduction in vascular complications. RAO occurs rarely with early deflation regardless of heparin dose. (Comparing TR Band to StatSeal in Conjunction With TR Band II [StatSeal II]; NCT04046952).

Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L.

The membrane-proximal external region (MPER) of HIV-1, located at the C terminus of the gp41 ectodomain, is conserved and crucial for viral fusion. Three broadly neutralizing monoclonal antibodies (bnMAbs), 2F5, 4E10, and Z13e1, are directed against linear epitopes mapped to the MPER, making this conserved region an important potential vaccine target. However, no MPER antibodies have been definitively shown to provide protection against HIV challenge. Here, we show that both MAbs 2F5 and 4E10 can provide complete protection against mucosal simian-human immunodeficiency virus (SHIV) challenge in macaques. MAb 2F5 or 4E10 was administered intravenously at 50 mg/kg to groups of six male Indian rhesus macaques 1 day prior to and again 1 day following intrarectal challenge with SHIV(Ba-L). In both groups, five out of six animals showed complete protection and sterilizing immunity, while for one animal in each group a low level of viral replication following challenge could not be ruled out. The study confirms the protective potential of 2F5 and 4E10 and supports emphasis on HIV immunogen design based on the MPER region of gp41.

Change in Invasively Measured Mean Pulmonary Artery Pressure After Transcatheter Mitral Valve Repair Is Associated With Heart Failure Readmission.

BACKGROUND: Pre-existing pulmonary hypertension is associated with poor outcomes after transcatheter mitral valve repair (TMVr) for mitral regurgitation (MR). However, the impact of an immediate change in mean pulmonary artery pressure (ΔmPAP) following TMVr on outcomes is unknown. METHODS: Patients who underwent TMVr from December 2015 to February 18, 2020 at our institution for symptomatic 3-4+ MR and who had invasive hemodynamics measured immediately pre- and post-TMVR were included. Multivariate Cox regression analysis was performed to examine the association of ΔmPAP (post-TMVr - pre-TMVr mPAP) with the primary endpoint of heart failure (HF) readmission at 1 year. Secondary endpoints included all-cause mortality and the composite endpoint of HF readmission or all-cause mortality at 1 year. RESULTS: Among 55 patients, 55% were men, mean age was 72 ± 14.2 years, and mean ΔmPAP was -1.4 ± 8.2 mm Hg. Overall, HF readmission occurred in 14 (25%), death in 10 (18%), and the composite endpoint in 20 (36%) patients. In multivariable analyses, higher ΔmPAP was significantly associated with HF readmission (hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00 - 1.21; P = 0.04). ΔmPAP was not associated with death (HR = 1.04, 95% CI: 0.96 - 1.14; P = 0.33), though there was a numerical but statistically non-significant trend towards the composite endpoint (HR = 1.06, 95% CI: 1.00 - 1.13; P = 0.06) driven by HF readmission. CONCLUSION: Higher ΔmPAP immediately following TMVr was associated with increased HF readmission at 1 year. Larger prospective studies are needed to validate these data and further explore the utility of ΔmPAP as a novel hemodynamic parameter to predict post-TMVR outcomes.

Impact of Cancer and Cardiovascular Disease on In-Hospital Outcomes of COVID-19 Patients: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

Background: While pre-existing cardiovascular disease (CVD) appears to be associated with poor outcomes in patients with Coronavirus Disease 2019 (COVID-19), data on patients with CVD and concomitant cancer is limited. Evaluate the effect of underlying CVD and CVD risk factors with cancer history on in-hospital mortality in those with COVID-19. Methods: Data from symptomatic adults hospitalized with COVID-19 at 86 hospitals in the US enrolled in the American Heart Association’s COVID-19 CVD Registry was analyzed. The primary exposure was cancer history. The primary outcome was in-hospital death. Multivariable logistic regression models were adjusted for demographics, CVD risk factors, and CVD. Interaction between history of cancer with concomitant CVD and CVD risk factors were tested. Results: Among 8222 patients, 892 (10.8%) had a history of cancer and 1501 (18.3%) died. Cancer history had significant interaction with CVD risk factors of age, body mass index (BMI), and smoking history, but not underlying CVD itself. History of cancer was significantly associated with increased in-hospital death (among average age and BMI patients, adjusted odds ratio [aOR]=3.60, 95% confidence interval [CI]: 2.07-6.24; p<0.0001 in those with a smoking history and aOR=1.33, 95%CI: 1.01 - 1.76; p=0.04 in non-smokers). Among the cancer subgroup, prior use of chemotherapy within 2 weeks of admission was associated with in-hospital death (aOR=1.72, 95%CI: 1.05-2.80; p=0.03). Underlying CVD demonstrated a numerical but statistically nonsignificant trend toward increased mortality (aOR=1.18, 95% CI: 0.99 - 1.41; p=0.07). Conclusion: Among hospitalized COVID-19 patients, cancer history was a predictor of in-hospital mortality. Notably, among cancer patients, recent use of chemotherapy, but not underlying CVD itself, was associated with worse survival. These findings have important implications in cancer therapy considerations and vaccine distribution in cancer patients with and without underlying CVD and CVD risk factors.

Impact of cancer and cardiovascular disease on in-hospital outcomes of COVID-19 patients: results from the american heart association COVID-19 cardiovascular disease registry.

BACKGROUND: While pre-existing cardiovascular disease (CVD) appears to be associated with poor outcomes in patients with Coronavirus Disease 2019 (COVID-19), data on patients with CVD and concomitant cancer is limited. The purpose of this study is to evaluate the effect of underlying CVD and CVD risk factors with cancer history on in-hospital mortality in those with COVID-19. METHODS: Data from symptomatic adults hospitalized with COVID-19 at 86 hospitals in the US enrolled in the American Heart Association's COVID-19 CVD Registry was analyzed. The primary exposure was cancer history. The primary outcome was in-hospital death. Multivariable logistic regression models were adjusted for demographics, CVD risk factors, and CVD. Interaction between history of cancer with concomitant CVD and CVD risk factors were tested. RESULTS: Among 8222 patients, 892 (10.8%) had a history of cancer and 1501 (18.3%) died. Cancer history had significant interaction with CVD risk factors of age, body mass index (BMI), and smoking history, but not underlying CVD itself. History of cancer was significantly associated with increased in-hospital death (among average age and BMI patients, adjusted odds ratio [aOR] = 3.60, 95% confidence interval [CI]: 2.07-6.24; p < 0.0001 in those with a smoking history and aOR = 1.33, 95%CI: 1.01-1.76; p = 0.04 in non-smokers). Among the cancer subgroup, prior use of chemotherapy within 2 weeks of admission was associated with in-hospital death (aOR = 1.72, 95%CI: 1.05-2.80; p = 0.03). Underlying CVD demonstrated a numerical but statistically nonsignificant trend toward increased mortality (aOR = 1.18, 95% CI: 0.99-1.41; p = 0.07). CONCLUSION: Among hospitalized COVID-19 patients, cancer history was a predictor of in-hospital mortality. Notably, among cancer patients, recent use of chemotherapy, but not underlying CVD itself, was associated with worse survival. These findings have important implications in cancer therapy considerations and vaccine distribution in cancer patients with and without underlying CVD and CVD risk factors.