Pre-existing Pulmonary Hypertension Research Articles

County health ranking: untangling social determinants of health and other factors associated with short-term bariatric surgery outcomes

BackgroundThe complex interplay of the social determinants of health, race/ethnicity, and traditional surgical risk factors on outcomes following metabolic surgery is poorly understood. ObjectiveTo evaluate the relationship between the social determinants of health as measured by county health ranking (CHR) and short-term metabolic surgery outcomes. SettingFive accredited bariatric program sites at a national academic health system. MethodsData were collected from 5 sites of a single health system from 2010 to 2021. Current procedural terminology codes identified primary and revisional cases. Patient characteristics, procedural data, and 30-day occurrences were collected. CHRs for health factors were determined by ZIP Code and stratified into best, middle, and worst terciles. The primary outcome was 30-day complications, readmissions, or reinterventions/reoperations. Logistic regression assessed the correlation between CHR tercile and morbidity. ResultsWe analyzed 4,315 primary and 370 revisional metabolic surgery cases. Overall, 64.0%, 27.4%, and 8.6% of patients lived in the best, middle, and worst CHR terciles, respectively. Patients in the middle and worst CHR terciles were more commonly older; non-Hispanic Black or Hispanic; suffered from preexisting chronic obstructive pulmonary disease or hypertension, were dialysis dependence, were on therapeutic anticoagulation, or had inferior vena cava filters. Middle and worst CHR tercile patients were more likely to undergo index sleeve gastrectomy or robotic-assisted surgery and have surgery performed by a self-designated general surgeon. Thirty-day outcomes were similar across CHR terciles. Racial disparity in multiple short-term outcomes persisted despite adjustment for CHR tercile. ConclusionHigher-risk patients are more likely to be from counties with lower CHRs, but CHR was not independently associated with 30-day outcomes after metabolic surgery.

COVID-19 and Pulmonary Hypertension: An Interesting Dynamic.

The dynamic between pulmonary hypertension (PH) and COVID-19 has been under investigation since 2020, early in the pandemic. Although the pathophysiology of PH has been well-studied, new discoveries regarding the multisystemic effects of COVID-19 are still being uncovered. The cardiopulmonary effects of COVID-19 have led investigators to inquire about the interplay between these 2 conditions. Several factors are suggested to contribute to an increased risk of developing PH after infection with SARS-CoV-2. This includes cytokine storm, acute respiratory distress syndrome, and fibrotic changes seen in post-COVID-19 lung disease. Additionally, it has been proposed that certain medications used to treat PH may be applied to patients suffering from the cardiopulmonary complications of COVID-19. This review will focus on the interplay between COVID-19 and PH, with a special focus on the risk of developing PH after SARS-CoV-2 infection and the outcomes of patients with preexisting PH who are diagnosed with COVID-19. The potential benefits of utilizing off-label PH medications for COVID-19 patients will also be discussed.

Pulsed-Field Ablation Does Not Worsen Baseline Pulmonary Hypertension Following Prior Radiofrequency Ablations

BackgroundStudies have reported development of pulmonary hypertension (PH) secondary to reduced LA compliance following AF ablation. ObjectivesThis study aimed to compare the risk of worsening of baseline PH between non-paroxysmal AF patients undergoing pulsed-field ablation (PFA) and standard radiofrequency ablation (RFA). MethodsThis multicenter study included 28 nonparoxysmal AF patients with PH undergoing a PFA-based ablation procedure after >1 failed RFA. A cohort of 28 AF patients with PH, scheduled for repeat RFA, 1:1 propensity-score matched using a multivariable logistic model, were used as the comparator group. Right heart catheterization and echocardiography were performed before and after the procedure to assess the pulmonary artery pressure (PAP). PH was defined as resting mean PAP of >20 mm Hg. ResultsThe baseline characteristics of the PFA and propensity-matched RFA groups were comparable. The mean PAP assessments at baseline, follow-up, and change from baseline were analyzed. The groups had comparable baseline mean pulmonary artery pressures (mPAP) (P = 0.177). After adjustment for baseline mPAP in an analysis of covariance model, the least-squares means change at 3 months after ablation was −1.71 ± 1.03 mm Hg and 19.67 ± 1.03 mm Hg in PFA and RFA, respectively (P <0.001). ConclusionsIn this propensity-matched population, no worsening of mPAP was detected following pulsed-field ablation in patients with pre-existing PH undergoing a repeat procedure for recurrence.

Hypercarbia and high-flow nasal oxygen use during anaesthesia - risking a failure to thrive?

Prevention of arterial oxygen desaturation during anaesthesia with high-flow nasal oxygen (HFNO) has gained greater acceptance for a widening range of procedures. However, during HFNO use there remains the potential for development of significant anaesthesia-associated apnoea or hypoventilation and the possibility of hypercarbia, with harmful cardiovascular or neurological sequelae. The aim of this study was to determine whether any HFNO-related hypercarbia adverse incidents had been reported on webAIRS, an online database of adverse anaesthesia-related incidents. Two relevant reports were identified of complications due to marked hypercarbia during HFNO use to maintain oxygenation. In both reports, HFNO and total intravenous anaesthesia were used during endoscopic procedures through the upper airway. In both, the extent of hypoventilation went undetected during HFNO use. An ensuing cardiac arrest was reported in one report, ascribed to acute hypercarbia-induced exacerbation of the patient's pre-existing pulmonary hypertension. In the other report, hypercarbia led to a prolonged duration of decreased level of consciousness post procedure, requiring ventilatory support. During the search, an additional 11 reports of postoperative hypercarbia-associated sedation were identified, unrelated to HFNO. In these additional reports an extended duration of severe acute hypercarbia led to sedation or loss of consciousness, consistent with the known effects of hypercarbia on consciousness. These 13 reports highlight the potential dangers of unrecognised and untreated hypercarbia, even if adequate oxygenation is maintained.

A new integrative approach combining right heart catheterization and echocardiography to stage aortic stenosis-related cardiac damage.

Although staging of the extent of aortic stenosis (AS)-related cardiac damages is usually performed via echocardiography, this technique has considerable limitations in assessing pulmonary artery and right chamber pressures. The present hypothesis-generating study sought to explore the efficacy of a staging system of cardiac damage based on echocardiographic and invasive [right heart catheterization (RHC)] hemodynamic parameters in patients undergoing transcatheter aortic valve implantation (TAVI). We studied 90 symptomatic patients with severe AS in whom echocardiographic and invasive evaluation by RHC was obtained prior to TAVI. Cardiac damage stages were defined as follows: no cardiac damage (stage 0), left ventricular (LV) damage (stage 1), left atrial or mitral valve damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), and right ventricular (RV) dysfunction or low-flow state (stage 4). With the integrative approach using RHC, pulmonary hypertension (PH) was defined as an mPAP ≥25 mmHg and the low-flow state corresponded to a cardiac index of <1.8 L/min/m2 and a right atrial pressure of >10 mmHg. During follow-up (median: 2.9 years), 43 patients (47.8%) died. The integrative cardiac damage staging was associated with a significant increase in all-cause and cardiovascular mortality per each increase of cardiac damage stage, whereas the outcome was similar according to the echocardiographic staging. A staging system of cardiac lesion based on echocardiographic and invasive hemodynamic parameters in patients with severe AS undergoing TAVI predicts mortality. Patients with pre-existing PH, ≥ moderate tricuspid regurgitation and/or RV dysfunction, and a low-flow state had a markedly increased risk of death. Further larger studies are needed to validate our findings.

Outcomes and characteristics of cardiac arrest in children with pulmonary hypertension: A secondary analysis of the ICU-RESUS clinical trial

BackgroundPrevious studies have identified pulmonary hypertension (PH) as a relatively common diagnosis in children with in-hospital cardiac arrest (IHCA), and preclinical laboratory studies have found poor outcomes and low systemic blood pressures during CPR for PH-associated cardiac arrest. The objective of this study was to determine the prevalence of PH among children with IHCA and the association between PH diagnosis and intra-arrest physiology and survival outcomes. MethodsThis was a prospectively designed secondary analysis of patients enrolled in the ICU-RESUS clinical trial (NCT02837497). The primary exposure was a pre-arrest diagnosis of PH. The primary survival outcome was survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1–3 or unchanged from baseline). The primary physiologic outcome was event-level average diastolic blood pressure (DBP) during CPR. ResultsOf 1276 patients with IHCAs during the study period, 1129 index IHCAs were enrolled; 184 (16.3%) had PH and 101/184 (54.9%) were receiving inhaled nitric oxide at the time of IHCA. Survival with favorable neurologic outcome was similar between patients with and without PH on univariate (48.9% vs. 54.4%; p = 0.17) and multivariate analyses (aOR 0.82 [95%CI: 0.56, 1.20]; p = 0.32). There were no significant differences in CPR event outcome or survival to hospital discharge. Average DBP, systolic BP, and end-tidal carbon dioxide during CPR were similar between groups. ConclusionsIn this prospective study of pediatric IHCA, pre-existing PH was present in 16% of children. Pre-arrest PH diagnosis was not associated with statistically significant differences in survival outcomes or intra-arrest physiologic measures.

Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters.

The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery represents one of the most challenging clinical scenarios. This fact mainly depends on the relationship existing between PH and right ventricular failure (RVF). Levosimendan (LS) is an inodilator that might be an effective agent in the treatment of PH and RVF. The aim of this study was to examine the impact of the duration of cardiopulmonary bypass (CPB) on the therapeutic drug monitoring of LS and to evaluate the effect of preemptive administration of LS on perioperative hemodynamic and echocardiographic parameters in cardiac surgical patients with preexisting PH. In this study, LS was administered in adult patients undergoing cardiac surgery before CPB in order to prevent exacerbation of preexisting PH and subsequent right ventricular dysfunction. Thirty cardiac surgical patients with preoperatively confirmed PH were randomized to receive either 6 μg/kg or 12 μg/kg of LS after the induction of anesthesia. The plasma concentration of LS was measured after CPB. In this study, a low sample volume was used combined with a simple sample preparation protocol. The plasma sample was extracted by protein precipitation and evaporated; then, the analyte was reconstituted and detected using specific and sensitive bioanalytical liquid chromatography with mass spectrometry (LC-MS/MS) methodology. The clinical, hemodynamic, and echocardiographic parameters were registered and evaluated before and after the administration of the drug. A fast bioanalytical LC-MS/MS methodology (a run time of 5.5 min) was developed for the simultaneous determination of LS and OR-1896, its main metabolite in human plasma. The LC-MS/MS method was linear over a range of 0.1-50 ng/mL for LS and 1-50 ng/mL for its metabolite OR-1896. Measured plasma concentrations of LS were inversely related to the duration of CPB. LS administration before CPB during cardiac surgery was effective in reducing pulmonary artery pressure and improving hemodynamic parameters after CPB, with a more pronounced and durable effect of the drug at the dose of 12 μg/kg. Additionally, administration of LS at a dose of 12 μg/kg in cardiac surgical patients with PH before CPB improved right ventricular function. LS administration decreases pulmonary artery pressure and may improve right ventricular function in patients with PH undergoing cardiac surgery.

Pulmonary hypertension, pulmonary embolism and COVID-19: A district general hospital experience from the UK.

Preliminary data suggest that the prevalence of pulmonary hypertension (PH) in patients with COVID-19 is around 13%, but its prognostic role remains unclear. Approximately 3% of patients develop chronic thrombo-embolic pulmonary hypertension (CTEPH) following diagnosis of acute pulmonary embolism (PE). It is recommended that patients are screened for CTEPH if they remain symptomatic 3 months following diagnosis of PE. The primary aim of the study was to assess the chances of persistent PH following PE secondary to COVID-19. We conducted a retrospective cohort study at a District General Hospital (DGH) in the United Kingdom. All patients diagnosed with COVID-19 and PE between April 2020 and October 2021 were examined. Patients were divided into two groups:·COVID-19 and PE with comorbidities (excluding pre-existing PH) and·COVID-19 and PE without comorbidities. We compared the ECHO features suggestive of PH between the two groups at the time of diagnosis of PE and at 3 months following treatment. 80 patients were included in the study (49 with comorbidities and 31 with no comorbidities). Average age of comorbidities and no comorbidities groups were 73 years and 70 years, respectively. Average PaO2/FiO2 ratio for comorbidities and no comorbidities groups were 170 and 195, respectively. Fourteen patients (13 with comorbidities and 1 with no comorbidities) died in total. Results showed that risk of persistent PH and subsequent mortality following PE in COVID-19 is 4.17 times and 1.32 times more in comorbidity group as compared to no comorbidity group, respectively (p < 0.001). Patients with comorbidities are at high risk of persistent PH and mortality due to PE secondary to COVID-19.

Diazoxide for Neonatal Hyperinsulinemic Hypoglycemia and Pulmonary Hypertension.

Hypoglycemia in neonates is associated with long-term neurodevelopmental effects. Hyperinsulinemic hypoglycemia (HH) is the most common cause of persistent hypoglycemia in neonatal intensive care units. Diazoxide is the only medication that is currently recommended for treatment of HH in neonates. However, the use of diazoxide in neonates is associated with pulmonary hypertension as an adverse effect. In this article, we review the literature on the mechanism of action and adverse effects with the use of diazoxide in neonatal hyperinsulinism. We then present a case series of neonates treated with diazoxide in our neonatal intensive care unit over a 5-year period. Among 23 neonates who received diazoxide, 4 developed pulmonary hypertension and 1 died. All infants who developed pulmonary hypertension were born preterm at less than 36 weeks gestation and had pre-existing risk factors for pulmonary hypertension. HH in preterm neonates, with pre-existing pulmonary hypertension or with risk factors for pulmonary hypertension requires thoughtful management.

Abstract 10384: Impact of Preexisting Pulmonary Hypertension on Outcomes in Patients Hospitalized With Covid-19

Introduction: Pulmonary hypertension (PH) is commonly associated with cardiopulmonary co-morbidities that increase morbidity and mortality risk with COVID-19. Hypothesis: This study aims to evaluate the association between preexisting PH and in-hospital outcomes in patients admitted with COVID-19. Methods: Consecutive patients at a large New England academic health system hospitalized with COVID-19 between March 1 and December 31, 2020, who had prior echocardiograms with documented estimated right ventricular systolic pressure (RVSP) were included. PH was defined as RVSP ≥30 mm Hg. Multivariable logistic regression adjusting for demographic and clinical characteristics was employed to relate PH to a primary outcome of all-cause mortality, and secondary outcomes including non-invasive positive pressure ventilation (NIPPV), myocardial infarction (MI), intensive care unit admission (ICU), and recurrent heart failure (HF) individually. Results: Of the 656 patients admitted, 395 (60.2%) had documented PH on a prior echocardiogram. PH patients were older, more likely to be men, and have cardiopulmonary and renal disease. Patients with PH had larger atrial size and higher E to early diastolic mitral annular tissue velocity (E/e') but similar left ventricular and right ventricular function compared to patients without PH. All-cause mortality (21% vs 10.3%, p= 0.001), need for ICU level of care (19% vs 13%, p = 0.046), NIPPV (23% vs 16%, p = 0.03), and recurrent HF (18% vs 5%, p &lt; 0.001) were more common in patients with PH compared to those without. Unadjusted and adjusted odds ratios relating PH to study outcomes appear in the Table . Conclusions: Preexisting PH is independently associated with higher risk of all-cause mortality in patients who are hospitalized with COVID-19.

Early Experience With Reverse Double Switch Operation for the Borderline Left Heart

This study reviews our early experience with the "reverse" double switch operation (R-DSO) for borderline left hearts. A retrospective review of children with borderline left hearts who underwent R-DSO between 2017 and 2021 was conducted. Patient characteristics and early hemodynamic and clinical outcomes were collected. R-DSO was performed in 8 patients with no operative or postoperative deaths; 5 underwent decompressing bidirectional Glenn. Left ventricular (LV) poor-compliance was the dominant pathophysiology. Four patients had undergone staged LV recruitment but were not candidates for anatomical biventricular circulation due to LV hypoplasia and/or diastolic dysfunction. 7/8 patients had risk factors for Fontan circulation including pulmonary vein stenosis, pulmonary hypertension, and pulmonary artery stenosis. Median age at R-DSO was 3.7 years (19 months-12 years). All patients were in sinus rhythm at discharge. At median follow-up of 15 months (57 days-4.1 years) no mortalities, reoperations or heart transplants had occurred. All patients had normal morphologic LV systolic function. In one patient, pre-existing pulmonary hypertension (HTN) resolved after R-DSO. Reinterventions included transcatheter mitral valve replacement for residual mitral stenosis and neo-pulmonary balloon valvuloplasty. In 4 patients follow-up catheterization done at a median of 519 days (320 days-4 years) demonstrated median cardiac index of 3.2 L/min/m2 (2.2-4); median sub-pulmonary left ventricular end diastolic pressure was 9 mm Hg (7-15); median inferior vena cava/baffle pressure was 8 mm Hg (7-13). R-DSO is an alternative to anatomical biventricular repair or single ventricle palliation in patients with borderline left hearts and can result in low inferior vena cava pressures and favorable early results. This approach can also relieve pulmonary HTN and allow future transplant candidacy.

AN INTERESTING CASE OF CARDIAC ARREST DURING THE CREATION OF AV FISTULA

TYPE: Case Report TOPIC: Cardiovascular Disease INTRODUCTION: We present an intersting case of cardiac arrest due to hemodynamic compromise occurring soon after AV fistula creation. CASE PRESENTATION: 45-year-old woman with medical history of ESRD on hemodialysis and pulmonary hypertension presented for left-arm AV fistula creation. Initial parts of the procedure went uneventful. However, towards the end of procedure, 10 minutes after unclamping of the graft, patient became hypotensive and suffered from cardiac arrest secondary to pulseless ventricular tachycardia progressing to torsades. Patient received CPR and multiple defibrillator shocks, epinephrine, IV magnesium sulfate and amiodarone boluses. Blood gas showed pH of 7.05 and lactate 6.5 mmol/L. Potassium, magnesium and phosphate levels were normal. She was started on epinephrine drip for hemodynamic support and heparin drip due to concern of PE. STAT TTE showed severe LVH with LVEF of 55 to 60%, moderate pulmonary hypertension, normal RV size and function. CTA of chest did not show any evidence of pulmonary embolism therefore heparin was stopped. Patient was transferred to ICU where she remained stable and had a full neurologic recovery. DISCUSSION: AV fistula creation in patients with pre-existing pulmonary hypertension and RV dysfunction could result in increased venous return and RV preload leading to acute RV dilatation. This could cause septal shift towards the left resulting in decreased LV preload, leading to decreased cardiac output, potentially resulting in hypotension. Decreased coronary and systemic perfusion could also result in myocardial ischemia and RV failure leading to arrhythmias and death. CONCLUSIONS: Physicians should be aware of this potentially fatal acute complication of AV fistula creation. DISCLOSURE: Nothing to declare. KEYWORD: Cardiac Arrest, AV Fistula, hemodynamic effects, dialysis access, high output cardiac failure

Reversal of pulmonary arterial hypertension and neointimal formation by kinin B1 receptor blockade

BackgroundThis study examined whether BI113823, a novel selective kinin B1 receptor antagonist can reverse established pulmonary arterial hypertension (PAH), prevent right heart failure and death, which is critical for clinical translation.MethodsLeft pneumonectomized male Wistar rats were injected with monocrotaline to induce PAH. Three weeks later, when PAH was well established, the rats received daily treatment of BI113823 or vehicle for 3 weeks.ResultsTreatment with BI113823 from day 21 to day 42 after monocrotaline injection reversed established PAH as shown by normalized values of mean pulmonary arterial pressure (mPAP). BI113823 therapy reversed pulmonary vascular remodeling, pulmonary arterial neointimal formation, and heart and lung fibrosis, reduced right ventricular pressure, right heart hypertrophy, improved cardiac output, and prevented right heart failure and death. Treatment with BI113823 reduced TNF-α and IL-1β, and macrophages recruitment in bronchoalveolar lavage, reduced CD-68 positive macrophages and expression of proliferating cell nuclear antigen (PCNA) in the perivascular areas, and reduced expression of iNOS, B1 receptors, matrix metalloproteinase (MMP)-2 and MMP-9 proteins, and the phosphorylation of ERK1/2 and AKT in lung. Treatment with BI113823 reduced mRNA expression of ANP, BNP, βMHC, CGTF, collange-I and IV in right heart, compared to vehicle treated controls. In human monocytes cultures, BI113823 reduced LPS-induced TNF-α production, MMP-2 and MMP-9 expression, and reduced TNF-α-induced monocyte migration.ConclusionsWe conclude that BI113823 reverses preexisting severe experimental pulmonary hypertension via inhibition of macrophage infiltration, cytokine production, as well as down regulation of matrix metalloproteinase proteins.

Twenty-year experience and outcomes in a national paediatric pulmonary hypertension service

Abstract Background/Introduction Paediatric pulmonary hypertension (PH) is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases (including several paediatric-specific aetiologies), contributions of different PH subtypes, therapeutic strategies and clinical outcomes in paediatric patients. Purpose In this study, we report the 20-year experience of a UK National Paediatric Pulmonary Hypertension Service focusing on the aetiology, management and outcomes of children with PH. Methods Consecutive patients presenting to the service between January 2001 and January 2021 were included in this retrospective study. Other inclusion criteria were: age ≤18 years at diagnosis and diagnosis of PH following specialist assessment. Only incident patients (without pre-existing PH) were entered in the survival analysis. Results A total of 1104 (81.5%) PH patients were included during the study period: 51% female, median age 2.6 [0.8–8.2] years. The most common PH diagnosis was group 1 (pulmonary arterial hypertension, PAH) in 532 (48.2%) patients, followed by group 3 PH (due to lung disease) in 358 (32.4%), group 2 (101, 9.1%), group 5 (93, 8.4%), and group 4 disease (20, 1.8%). The most common PAH subgroup was PAH associated with congenital heart disease (CHD, 63.3%), followed by idiopathic PAH (22.4%). One quarter of patients (23.6%) had multiple contributory factors for PH, fitting more than one diagnostic group. Resolution of PH, defined as normalisation of pulmonary artery pressures following cessation of PAH therapy, occurred in 172 (15.6%) patients at a median age of 3.7 [2.1–5.7] years and was more common in group 3 than other PH groups (33.5% vs. 9.1% at 5 years post-diagnosis, p&amp;lt;0.0001). Overall, 909 (82.3%) patients received PAH therapy. Patients with group 3 PH were as likely to receive PAH therapy as an initial treatment strategy as group 1 patients (86.6% vs. 82.3%, p=0.11), but were more likely to receive sildenafil monotherapy (p=0.002) and less likely to be offered triple therapy (p&amp;lt;0.0001). During follow-up, maintenance or escalation to triple therapy was required in 103 (9.3%) patients and was far more common in idiopathic compared to other PAH subgroups (37.7% vs. 7.8%, p&amp;lt;0.0001). Transplant-free survival was 86.7% (95% CI: 84.5–88.9%) at 1 year, 74.2% (95% CI: 71.1–77.5%) at 5 years, and 68.9% (95% CI: 65.1–73%) at 10 years (Figure 1). PAH related to CHD had the highest transplant-free survival (HR 0.62, 95% CI: 0.46–0.84, p=0.002). Group 2 had the lowest transplant-free survival (HR 2.09, 95% CI: 1.42–3.09, p=0.0002) whereas groups 3,4 and 5 did not differ significantly from PAH (Figure 2). Conclusions In this large, national cohort of paediatric PH patients, the most common type of PH was PAH, followed by group 3 PH. Multiple contributory causes for PH are common and PH resolution was not uncommon, especially in group 3 patients. Despite widespread use of PAH therapy, the prognosis remains guarded. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Constantine has received a PhD grant from Janssen-Cilag Ltd. as the CHAMPION PhD Fellow. Figure 1Figure 2

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

BackgroundPre-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.MethodsPatients 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.ResultsAmong 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.ConclusionHigher 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.

Evaluation of endothelial dysfunction and clinical events in patients with early-stage vasculopathy in limited systemic sclerosis.

Limited cutaneous systemic sclerosis (lcSSc) is characterised by vasculopathy contributing to vascular apoptosis, structural and functional changes. The aim of this study was to investigate parameters of endothelial dysfunction and their association to clinical events in lcSSc patients with early-stage vasculopathy. Patients with lcSSc and early-stage vasculopathy defined as absent pre-existing pulmonary arterial hypertension (PAH), digital ulcers, and symptomatic cardiovascular diseases were recruited together with age-, race- and sex-matched controls with primary Raynaud's phenomenon. All subjects underwent measurements of flow-mediated (FMD) and nitroglycerine-mediated dilation (NMD), pulse-wave analysis, and biochemical analysis, including arginine, homoarginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and endothelial microparticles (EMP). Clinical events, including EUSTAR index, sicca symptoms, microvascular, skin, renal, gastrointestinal, and pulmonary involvement, were recorded by medical history, physical examination, laboratory parameters, disease-specific questionnaire, electrocardiogram, diagnostic imaging and spirometry. 38 patients with lcSSc and 38 controls were included after screening for eligibility. There was no difference in FMD (p=0.775), NMD (p=0.303), aortic pulse-wave velocity (p=0.662) or in augmentation index (p=0.600) between patients with lcSSc and controls. Higher values of ADMA (p=0.030), SDMA (p=0.025) and borderline significantly higher values for CD31+/CD42b- EMP (p=0.062) were observed in lcSSc patients, also with positive correlations between those parameters. ADMA, SDMA and CD31+/CD42b- were correlated with subclinical PAH, nephropathy and capillary changes. Selected parameters of endothelial dysfunction contribute to clinical events in lcSSc patients with early-stage vasculopathy and endothelial dysfunction seems to be primarily present in microvasculature, while its impact on macrovascular changes in lcSSc is still indistinct.

AMPK and Pulmonary Hypertension: Crossroads Between Vasoconstriction and Vascular Remodeling.

Pulmonary hypertension (PH) is a debilitating and life-threatening disease characterized by increased blood pressure within the pulmonary arteries. Adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric serine-threonine kinase that contributes to the regulation of metabolic and redox signaling pathways. It has key roles in the regulation of cell survival and proliferation. The role of AMPK in PH is controversial because both inhibition and activation of AMPK are preventive against PH development. Some clinical studies found that metformin, the first-line antidiabetic drug and the canonical AMPK activator, has therapeutic efficacy during treatment of early-stage PH. Other study findings suggest the use of metformin is preferentially beneficial for treatment of PH associated with heart failure with preserved ejection fraction (PH-HFpEF). In this review, we discuss the “AMPK paradox” and highlight the differential effects of AMPK on pulmonary vasoconstriction and pulmonary vascular remodeling. We also review the effects of AMPK activators and inhibitors on rescue of preexisting PH in animals and include a discussion of gender differences in the response to metformin in PH.

Detrimental effects of elevated transpulmonary gradient on outcomes following restrictive mitral annuloplasty in patients with pre-existing pulmonary hypertension.

BackgroundThis study retrospectively examined the association between elevated trans-pulmonary gradient (TPG), which reflects pre-capillary contribution to pulmonary hypertension (PH), and postoperative pulmonary hemodynamics and outcomes following restrictive mitral annuloplasty (RMA) in patients with pre-existing PH.MethodsPre- and postoperative (1 month) cardiac catheterization was performed in 64 patients with severely impaired left ventricular function (i.e., ejection fraction ≤40%) and pre-existing PH (mean pulmonary artery pressure (PAP) ≥25 mmHg) who underwent RMA. Patients were segregated into two groups: low TPG (≤12 mmHg) and elevated TPG (>12 mmHg). The mean follow-up period was 54±27 months. The primary outcome seen was a change in pulmonary hemodynamics after RMA; secondary outcomes were composite adverse events, including all-cause mortality and readmission for heart failure.ResultsCompared to the low TPG group, patients in the elevated TPG group were more likely to show a postoperative mean PAP of ≥25 mmHg (84% vs. 38%), TPG of >12 mmHg (79% vs. 11%), and pulmonary vascular resistance of ≥240 dynes/sec/cm−5 (84% vs. 6.7%) (all P<0.001), although both groups showed comparable degrees of mitral regurgitation improvement. Serial echocardiography demonstrated that Doppler-derived systolic PAP, which once decreased in both groups, remained stable in the low group while steadily increasing in the elevated group (group effect P<0.001). Patients with elevated TPG had lower freedom from composite adverse events (5-year, 20% vs. 70%, P=0.003). After adjusting for baseline covariates, the elevated TPG was independently associated with increased risk of adverse events (adjusted hazard ratio 2.9, 95% CI: 1.2–6.9, P=0.017).ConclusionsElevated TPG negatively affects postoperative pulmonary hemodynamics and late outcomes in patients with advanced cardiomyopathy and pre-existing PH who have undergone RMA. These findings suggest that the assessment of TPG should be included in post-RMA risk stratification.

Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry.

Pulmonary hypertension (PH) is a life-shortening condition characterised by episodes of decompensation precipitated by factors such as disease progression, arrhythmias and sepsis. Surgery and pregnancy also place additional strain on the right ventricle. Data on critical care management in patients with pre-existing PH are scarce.We conducted a retrospective observational study of a large cohort of patients admitted to the critical care unit of a national referral centre between 2000–2017 to establish acute mortality, evaluate predictors of in-hospital mortality and establish longer term outcomes in survivors to hospital discharge.242 critical care admissions involving 206 patients were identified. Hospital survival was 59.3%, 94% and 92% for patients admitted for medical, surgical or obstetric reasons, respectively. Medical patients had more severe physiological and laboratory perturbations than patients admitted following surgical or obstetric interventions. Higher APACHE II (Acute Physiology and Chronic Health Evaluation) score, age and lactate, and lower oxygen saturation measure by pulse oximetry/inspiratory oxygen fraction (SpO2/FiO2) ratio, platelet count and sodium level were identified as independent predictors of hospital mortality. An exploratory risk score, OPALS (oxygen (SpO2/FiO2) ≤185; platelets ≤196×109·L−1; age ≥37.5 years; lactate ≥2.45 mmol·L−1; sodium ≤130.5 mmol·L−1), identified medical patients at increasing risk of hospital mortality. One (11%) out of nine patients who were invasively ventilated for medical decompensation and 50% of patients receiving renal replacement therapy left hospital alive. There was no significant difference in exercise capacity or functional class between follow-up and pre-admission in patients who survived to discharge.These data have clinical utility in guiding critical care management of patients with known PH. The exploratory OPALS score requires validation.

TRICUSPID VALVE REGURGITATION IN PATIENTS UNDERGOING ENDOCARDIAL LEADS PLACEMENT

Objective: To assess prospectively the presence and degree of tricuspid regurgitation (TR) after right ventricular (RV) lead placement utilizing 2-dimensional and doppler echocardiography in a group of patients implanted with Permanent pace-maker or implantable cardioverter defibrillator (ICD).&#x0D; Study Design: Descriptive cross sectional study.&#x0D; Place and Duration of Study: Study was conducted at OPD of AFIC/NIHD Rawalpindi from Jan to Jun 2019.&#x0D; Methodology: One hundred patients after cardiac stimulation system implantation were included in this study. Patients with severe valve disease, heart failure, congenital heart disease, pre-existing pulmonary hypertension and presence of moderate or severe tricuspid regurgitation were excluded. M-mode, 2 –dimensional and doppler echocardiographic studies were performed. Continuous-wave doppler measurements were made from apical four-chamber view in order to obtain maximum tricuspid flow velocities. A complete echocardiographic study was performed following device implantation. Echocardiographic measurements were repeated at 6-months of follow-up period. Those patients who developed tricuspid regurgitation were further assessed by color doppler, taking into account density and contour of the jet on continuous-wave doppler. Tricuspid regurgitation severity was classified into three groups: mild, moderate and severe according to the recommendations for non-invasive evaluation of native valvular regurgitation by the American Society of Echocardiography. The collected data was analysed by using SPSS-23.&#x0D; Results: Out of 100 patients, 67 (67%) were males and 33(33%) were females with the mean age of 65.29 ± 12.02 years. All the patients had normal chambers dimensions before the procedure. 65 (65%) had leads screwed to RV apex while 35 (35%) had through RV septum. 83 (83%) patients received a dual chamber device, while 17 (17%) patients got single chamber (ventricular) device implanted. Following device implantation after 6 months mild TR was noted in 4 (4%), moderate TR in 4 (4%) and severe TR 2 (2%) in cases.&#x0D; Conclusion: Tricuspid incompetence following endocardial leads implantation is not rare and occurred in approximately 10% of our patients. This complication may be preventable, because it is likely due to the interference of the endocardial lead with the TV.