Post-capillary Pulmonary Hypertension Research Articles

Elucidating the Clinical Implications and Pathophysiology of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Call to Action: A Science Advisory From the American Heart Association.

This science advisory focuses on the need to better understand the epidemiology, pathophysiology, and treatment of pulmonary hypertension in patients with heart failure with preserved ejection fraction. This clinical phenotype is important because it is common, is strongly associated with adverse outcomes, and lacks evidence-based therapies. Our goal is to clarify key knowledge gaps in pulmonary hypertension attributable to heart failure with preserved ejection fraction and to suggest specific, actionable scientific directions for addressing such gaps. Areas in need of additional investigation include refined disease definitions and interpretation of hemodynamics, as well as greater insights into noncardiac contributors to pulmonary hypertension risk, optimized animal models, and further molecular studies in patients with combined precapillary and postcapillary pulmonary hypertension. We highlight translational approaches that may provide important biological insight into pathophysiology and reveal new therapeutic targets. Last, we discuss the current and future landscape of potential therapies for patients with heart failure with preserved ejection fraction and pulmonary vascular dysfunction, including considerations of precision medicine, novel trial design, and device-based therapies, among other considerations. This science advisory provides a synthesis of important knowledge gaps, culminating in a collection of specific research priorities that we argue warrant investment from the scientific community.

Apolipoprotein A1 is associated with pulmonary vascular resistance and adverse clinical outcomes in patients with pulmonary hypertension secondary to heart failure.

Pulmonary hypertension secondary to heart failure (HF‐PH) combined with pulmonary vascular remodeling has a high mortality rate. Apolipoprotein A1 (ApoA1) has been shown to adversely affect outcomes in patients with HF. A prospective follow‐up study was performed on 239 consecutive patients with HF‐PH who underwent right heart catheterization. Proteomics technology was used to analyze different proteins in plasma between post‐ and precapillary pulmonary hypertension (CpcPH) and isolated postcapillary pulmonary hypertension (IpcPH) filtered by propensity score matching. Ultimately, 175 patients were enrolled and followed for an average of 4.4 years. Lipoprotein components in plasma were measured, and the following clinical events were tracked. Proteomics data showed that lipid metabolism and inflammation were different between CpcPH and IpcPH. ApoA1 levels in HF‐PH patients with CpcPH were lower than those in HF‐PH patients with IpcPH. The patients with lower ApoA1 levels (≤1.025 g/L) were in a higher New York Heart Association class and had high levels of NT‐proBNP, mean pulmonary artery pressure, PVR, and diastolic pressure gradient. Besides, HF‐PH patients with lower ApoA1 levels had a 2.836‐fold higher relative risk of comorbid CpcPH compared with patients with higher ApoA1 levels. Moreover, patients with lower ApoA1 levels had a lower survival rate after adjusting for CpcPH. In conclusion, ApoA1 levels were negatively correlated with PVR levels. Lower ApoA1 levels were an independent risk factor for pulmonary vascular remodeling in HF‐PH patients. The survival of HF‐PH patients with lower ApoA1 levels was reduced.

Cine magnetic resonance imaging detects shorter cardiac rest periods in postcapillary pulmonary hypertension.

A shorter cardiac rest period within a cardiac cycle is usually thought to be a result of a fast heart rate, and its clinical relevance has long been ignored. The aim of the present study was to test the hypothesis that the length of cardiac rest periods is altered in postcapillary pulmonary hypertension (PH). Twenty-six patients with postcapillary PH and 20 healthy controls were recruited for cardiac magnetic resonance imaging (MRI) scans. All participants had a heart rate no higher than 80 beats/minute. Cine magnetic resonance imaging (MRI, acquired at a four-chamber view) was analyzed to determine the length of cardiac rest periods at end-systole and mid-to-late diastole. PH patients had a shorter rest period at mid-to-late diastole than controls (17.5 ± 8.7% vs. 24.2 ± 4.2%, P = 0.003). Receiver operating characteristic (ROC) curves showed that the proportion of the rest period in diastole (defined as the length of diastasis/diastole) can discriminate PH patients from controls [area under the curve (AUC) = 0.83, 95% confidence interval (CI): 0.71-0.96]. The existence of postcapillary PH was a significant contributor (β = -5.537, P = 0.023) to shorter cardiac rest periods at mid-to-late diastole after adjusting for potential confounders, including age, sex, heart rate, and blood pressure. Postcapillary PH is independently associated with shorter cardiac rest periods at mid-to-late diastole. The length of cardiac rest periods has the potential to become a novel quantitative imaging biomarker for indicating cardiovascular health.

Normalization of Four Different Types of Pulmonary Hypertension After Atrial Septal Defect Closure.

Pulmonary hypertension (PH) is an established risk factor in patients with atrial septal defect (ASD), and its persistence after ASD closure is associated with increased mortality. Therefore, predictors for PH normalization after defect closure are needed. Multiple hemodynamic types of PH exist, but little is known about their prevalence and prognostic value for PH normalization after ASD closure. We carried out a retrospective study on 97 patients (76% female, median age at ASD closure 58 years) with four types of PH determined predominantly by right heart catheterization: hyperkinetic, pulmonary arterial hypertension, isolated post-capillary, and combined pre- and post-capillary. We investigated the frequency of the PH types and their prognostic significance for PH normalization after ASD closure. Frequency of PH types before ASD closure in our study was: hyperkinetic 55%, pulmonary arterial hypertension 10%, isolated post-capillary PH 24%, and combined PH 11%. Hyperkinetic PH type was positively associated with PH normalization after ASD closure (78% patients normalized), remaining a significant independent predictor when adjusted for age at closure, sex, heart failure, and NYHA. Hyperkinetic PH patients also had significantly better survival prognosis versus patients with other PH types (p = 0.04). Combined PH was negatively associated with PH normalization, with no patients normalizing. Pulmonary arterial hypertension and isolated post-capillary PH had intermediate rates of normalization (60 and 52%, respectively). In summary, all four hemodynamic types of PH are found in adult patients with ASD, and they can be used to stratify patients by their likelihood of PH normalization and survival after ASD closure.

Cardiac and Hemodynamic Manifestations of Hereditary Hemorrhagic Telangiectasia.

The autosomal dominant trait hereditary hemorrhagic telangiectasia (HHT) causes multiorgan dysplastic lesions of the vasculature that can activate multiple physiological cascades leading to a broad array of cardiovascular diseases. Up to 78% of patients with HHT develop hepatic arteriovenous malformations (AVMs), which cause a hyperdynamic circulatory state secondary to hepatic/portal shunting. This condition can eventually progress to high-output cardiac failure (HOCF) with continued peripheral tissue hypoxemia. Treatment for HOCF is often limited to supportive measures (diuretics and treatment of anemia); however, recent studies using systemic bevacizumab have shown promise by substantially reducing the cardiac index. In the context of liver AVMs and high cardiac output, the pulmonary vasculature can also experience high flow. Without adequate dilation of pulmonary vessels, post-capillary pulmonary hypertension can develop. Another form of pulmonary hypertension observed in HHT, pulmonary arterial hypertension, is caused by HHT-related mutations in ENG and ACVRL1 causing congestive arteriopathy. Post-capillary pathogenesis is addressed by reducing the high-output state, whereas the pre-capillary state is treated with supportive mechanisms (diuretics, oxygen) and agents targeting pulmonary vasoreactivity: endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors. If either form of pulmonary hypertension is left untreated or proves refractory and progresses, the common hemodynamic complication is right heart failure. Targeted right heart therapies involve similar strategies to those of pulmonary arterial hypertension, with several experimental approaches under study. In this review, we describe in detail the mechanisms of pathogenesis, diagnosis, and treatment of the hemodynamic complications and associated cardiovascular diseases that may arise in patients with HHT.

Combined pre- and post-capillary pulmonary hypertension in left heart disease.

Patients with heart failure (HF) often have pulmonary hypertension (PH), which is mainly post-capillary; however, some of them also develop a pre-capillary component. The exact mechanisms leading to combined pre- and post-capillary PH are not yet clear, but the phenomenon seems to start from a passive transmission of increased pressure from the left heart to the lungs, and then continues with the remodeling of both the alveolar and vascular components through different pathways. More importantly, it is not yet clear which patients are predisposed to develop the disease. These patients have some characteristics similar to those with idiopathic pulmonary arterial hypertension (e.g., young age and frequent incidence in female gender), but they share cardiovascular risk factors with patients with HF (e.g., obesity and diabetes), with both reduced and preserved ejection fraction. Thanks to echocardiography parameters and newly introduced scores, more tools are available to distinguish between idiopathic pulmonary arterial hypertension and combined PH and to guide patients' management. It may be hypothesized to treat patients in whom the pre-capillary component is predominant with specific therapies such as those for idiopathic pulmonary arterial hypertension; however, no adequately powered trials of PH-specific treatment are available in combined PH. Early evidence of clinical benefit has been proven in some trials on phosphodiesterase type 5 inhibitors, while data on prostacyclin analogues, endothelin-1 receptor antagonists, and soluble guanylate cyclase stimulators are still controversial.

Beneficial Effects of Pulmonary Vasodilators on Pre-Capillary Pulmonary Hypertension in Patients with Chronic Kidney Disease on Hemodialysis.

Background: In patients with chronic kidney disease (CKD) on hemodialysis, comorbid pulmonary hypertension (PH) aggravates exercise tolerance and eventually worsens the prognosis. The treatment strategy for pre-capillary PH, including combined pre- and post-capillary PH (Cpc-PH), has not been established. Objectives: This study aimed to evaluate the impact of pulmonary vasodilators on exercise tolerance and pulmonary hemodynamics in patients with CKD on hemodialysis. Methods and Results: The medical records of 393 patients with suspected PH who underwent right heart catheterization were reviewed. Of these, seven patients had isolated pre-capillary PH and end-stage CKD on hemodialysis. Pulmonary vasodilators decreased pulmonary vascular resistance from 5.9 Wood units (interquartile range (IQR), 5.5–7.6) at baseline to 3.1 Wood units (IQR, 2.6–3.3) post-treatment (p = 0.02) as well as increased pulmonary capillary wedge pressure from 10 mmHg (IQR, 7–11) to 11 mmHg (IQR, 8–16) (p = 0.04). Pulmonary vasodilators increased the World Health Organization functional class I or II from 0% to 100% (p = 0.0002) and the 6 min walk distance from 273 m (IQR, 185–365) to 490 m (IQR, 470–550) (p = 0.03). Conclusions: Pulmonary vasodilators for PH in patients with CKD on hemodialysis decrease pulmonary vascular resistance and eventually improve exercise tolerance. Pulmonary vasodilators may help hemodialysis patients with pre-capillary PH, although careful management considering the risk of pulmonary edema is required.

P234 A RARE CASE OF ACUTE RIGHT HEART FAILURE PRESENTED IN A CASE REPORT

Abstract Case Summary A 62–year–old male with multiple cardiovascular risk factors, presented at the ED with signs and symptoms of right heart failure, Doppler echocardiography showed a severe dilatation and dysfunction of the right ventricle and left ventricular diastolic dysfunction. After initial stabilization with diuretics and inotropes, the patient performed a coronary angiogram with evidence of severe multivessel coronary artery disease and combined pre–capillary and post–capillary pulmonary hypertension as shown by the right heart catheterization. After complete revascularization, the diastolic function of the left ventricle improved dramatically, and the right ventricle recovered completely. Discussion We presented a paradigmatical case of acute right heart failure secondary to left ventricular diastolic impairment in a patient affected by severe ischemic coronary artery disease. Several risk factors are associated with RVD in HFpEF: atrial fibrillation, male sex, chronic obstructive pulmonary disease. Diastolic performance of the LV is one of the main determinants of the right ventricular function, which, in turn, is proven to have prognostic implication in HFpEF. Nowadays, there is no evidence–based treatment for right heart failure secondary to decompensated HFpEF and therapy should be tailored to the individual patient’s response.

P416 A NOT–SO–RARE COMPLICATION OF CONNECTIVE TISSUE DISEASE

Abstract Pulmonary hypertension is a not–so–rare complication of connective tissue diseases and is usually related with an inauspicious prognosis.We present the case of a 67–years–old woman hospitalized for progressive dyspnea. Two–dimensional echocardiography showed numerous features related to pulmonary hypertension (PH) with moderate Mitral Regurgitation. The right cardiac catheterization confirmed mixed PH (pre and post capillary) without chest angio–TC evidence of pulmonary thromboembolism. Thanks to optimized medical therapy (B–Blocker, ACE–i and diuretics), there was a significant clinical improvement documented at discharge. After 1 year, due to recurrence of dyspnea, she was admitted to our medical unit. Her clinical examination showed some of the characteristics of a connective tissue disease. Compared to previous echocardiography, a moderate to mild reduction of MR was documented. Chest CT scan revealed interstitial lung disease likely related to patient’s underlying pathology. Immunological screening tests detected the presence of antinuclear (ANA) and anti–topoisomerase (ATA) antibodies. Right heart catheterization documented a worsening of PH with only pre–capillary component. On the basis of the above findings, a diagnosis of CREST syndrome complicated with PH was made, and the patient was started on oral combination of macitentan and riociguat. The frequency of this complication in connective tissue disease, the need for screening tests and different treatment approaches of pre and post capillary pulmonary hypertension is discussed.

C33 PERCUTANEOUS CLOSURE OF MITRAL PARAVALVULAR LEAK (PVL): WHEN REVERSAL MAKES ALL THE DIFFERENCE

Abstract PVL is a complication associated with the implantation of a prosthetic valve. Since surgical re–intervention has a high operative risk, percutaneous closure (PC) has emerged due to its reduced invasiveness and the development of dedicated materials. We describe the case of a 66–year–old man with a mechanical oscillating disc mitral prosthesis who was admitted for acute heart failure. An echo showed a left ventricle with normal motion and a postero–medial mitral PVL with significant regurgitation. A transoesophageal echo confirmed the PVL in the 5 o’clock viewing portal with severe regurgitation. After optimising the medical therapy and with no change in echo findings, a cardiac catheterisation showed persistent post–capillary pulmonary hypertension, and therefore PC of the PVL was scheduled. Given the postero–medial location of the PVL, a transseptal puncture was performed using a 8.5 Fr Agilis introducer (Terumo) with telescoping system of a 6 r. JR4 catheter. The PVL was passed through with a Terumo 0.035 J–shaped guide, but without managing to advance the catheter beyond the leak. The guide was therefore advanced into the abdominal aorta and an arteriovenous circuit was created, which allowed the catheter to be advanced beyond the PVL and a closure device (AVPIII 14/5,Abbott St.Jude) was positioned with anterograde placement, with a distal disc on the ventricular side. Obliteration of the PVL, interference with the prosthetic disc and high transprosthetic gradients were observed despite several attempts to relocate the AVP, which was therefore removed. A second procedure was performed at a distance, creating a similar arteriovenous circuit by using a long introducer (110cm–Cook) which was advanced from the femoral artery beyond the leak in the opposite direction. An AVPIII (12/5) with a distal disc on the atrial side was positioned, this time with retrograde placement, with effective closure of the PVL and minimal residual regurgitation, without interference with the prosthesis. The course was free of complications; after one month the echo confirmed the result. Transcatheter closure of the PVL is a complex procedure, but relatively safe in experienced hands. This case is of particular interest due to the difficulty presented by the location of the PVL, which required measures of high technical complexity and because it describes a possible complication of the procedure, which was resolved by the simple reversal of the placement of the device.

Patient–Prosthesis Mismatch Associated With Somatic Growth After Mechanical Mitral Valve Replacement in Small Children: Metrics for Reoperation and Outcomes

Reoperation after pediatric mitral valve replacement (MVR) is inevitable due to patient-prosthesis mismatch (PPM) associated with somatic growth. We analyzed potential metrics for PPM and outcomes of redo MVR for valve upsizing. Between 1999 and 2018, 15 children without obstructive left heart lesions other than mitral stenosis underwent initial MVR with a 16-mm ATS-Advanced Performance valve. We analyzed hemodynamic data from 28 postoperative catheterizations and concomitant echocardiograms. The median age and body weight at initial MVR were 4.9 months (25th, 75th percentile: 3.6, 6.6) and 5.9 kg (5.0, 7.3). Redo MVR was planned when patients had congestive heart failure and postcapillary pulmonary hypertension (PH) due to PPM: systolic pulmonary arterial pressure (SPAP) >35 mm Hg and pulmonary capillary wedge pressure (PCWP) >15 mm Hg on catheterization. Indexed effective orifice area (iEOA) and mean transmitral pressure gradient (TMPG) were strongly correlated with SPAP (r = -0.72, P < 0.001 and r = 0.75, P < 0.001) and PCWP (r = -082, P < 0.001 and r = 0.84, P < 0.001). Cut-off values for detecting postcapillary PH due to PPM were 1.0 cm2/m2 for iEOA and 18 mm Hg for mean TMPG. Nine patients underwent redo MVR for postcapillary PH due to PPM at a median postoperative interval of 10 years (9.2, 11.9). All the patients survived, and PH was improved one year after surgery. iEOA and mean TMPG can be metrics for PPM in children after MVR. Careful follow-up is required to confirm the improvement of preoperatively existing PH after redo MVR for valve upsizing.

Pulmonary Vascular Reverse Remodeling After Left Ventricular Assist Device Implantation in Patients With Pulmonary Hypertension.

Prevalence of combined pre- and post-capillary (Cpc) pulmonary hypertension (PH) in patients with PH due to left heart disease (PH-LHD) and the long-term impact of left ventricular assist device (LVAD) implantation in patients with Cpc-PH are not fully elucidated. Eighty-nine patients with PH-LHD who underwent LVAD implantation were retrospectively analyzed. Patients were divided into two groups according to their preoperative pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG) values (Cpc-PH group, PVR >3 wood units [WU], or DPG ≥7 mmHg; isolated postcapillary [Ipc]-PH group, PVR ≤3 WU, and DPG <7 mmHg). There were 50 patients with Cpc-PH (PVR >3 WU [group A, n = 41]; PVR >3 WU and DPG ≥7 mmHg [group B, n = 8]; DPG ≥7 mmHg [group C, n = 1]), and 39 patients with Ipc-PH. Despite a successful LVAD implantation in all participants, 13 and two patients remained in groups A and B, respectively, early after LVAD implantation, whereas two patients each remained in groups A and B 1 year postoperatively. Values of PVR and DPG in the Cpc-PH group returned to normal levels by 3 years postoperatively. Over 50% of patients with PH-LHD had Cpc-PH, and PVR and DPG normalized in all participants within 3 years after LVAD implantation.

Impact of Esophageal Pressure Measurement on Pulmonary Hypertension Diagnosis in Patients With Obesity

Elevated intrathoracic pressure could affect pulmonary vascular pressure measurements and influence pulmonary hypertension (PH) diagnosis and classification. Esophageal pressure (Pes) measurement adjusts for the increase in intrathoracic pressure, better reflecting the pulmonary hemodynamics in patients with obesity. In individuals with obesity, what is the impact of adjusting pulmonary hemodynamic determinations for Pes on PH diagnosis and classification? Can Pes be estimated by positional or respiratory hemodynamic changes? In this prospective cohort study, we included patients with obesity who underwent right heart catheterization and demonstrated elevated pulmonary artery wedge pressure (PAWP;≥ 12mmHg). After placement of an esophageal balloon, we performed pressure determination using an air-filled transducer connected to a regular hemodynamic monitor. We measured pulmonary pressures changes when sitting and the variations during the respiratory cycle. We included 53 patients (mean ± SD age, 59 ± 12 years; mean ± SD BMI, 44.4 ± 10.2kg/m2). Supine end-expiratory pressures revealed a mean pulmonary artery pressure of > 20mmHg in all patients and a PAWP of >15mmHg in most patients (n= 50). The Pes adjustment led to a significant decrease in percentage of patients with postcapillary PH (from 60%to 8%) and combined precapillary and postcapillary PH (from 34%to 11%), at the expense of an increase in percentage of patients with no PH (0%to 23%), isolated precapillary PH (2%to 25%), and undifferentiated PH (4%to 34%). Adjusting pulmonary hemodynamics for Pes in patients with obesity leads to a pronounced reduction in the number of patients who receive a diagnosis of postcapillary PH. Measuring Pes should be considered in patients with obesity, particularly those with elevated PAWP.

Noninvasive diagnosis of pulmonary hypertension with hyperpolarised 129Xe magnetic resonance imaging and spectroscopy.

BackgroundThe diagnosis of pulmonary hypertension (PH) remains challenging. Pre- and post-capillary PH have different signatures on noninvasive 129Xe gas-exchange magnetic resonance imaging (MRI) and dynamic MR spectroscopy (MRS). We tested the accuracy of 129Xe MRI/MRS to diagnose PH status compared to right heart catheterisation (RHC).Methods129Xe MRI/MRS from 93 subjects was used to develop a diagnostic algorithm, which was tested in 32 patients undergoing RHC on the same day (n=20) or within 5 months (42±40 days) (n=12). Three expert readers, blinded to RHC, used 129Xe MRI/MRS to classify subjects as pre-capillary PH, post-capillary PH, no PH and no interstitial lung disease (ILD), or ILD.ResultsFor pre-capillary PH, 129Xe MRI/MRS diagnostic accuracy was 75% (95% CI 66–84) with a sensitivity of 67% (95% CI 54–79) and a specificity of 86% (95% CI 75–96); for post-capillary PH accuracy was 69% (95% CI 59–78) with sensitivity of 54% (95% CI 34–74) and specificity of 74% (95% CI 63–84). The model performed well in straightforward cases of pre-capillary PH but was less accurate in its diagnosis in the presence of mixed disease, particularly in the presence of ILD or combined post- and pre-capillary PH.ConclusionThis study demonstrates the potential to develop 129Xe MRI/MRS into a modality with good accuracy in detecting pre- and post-capillary PH. Furthermore, the combination of 129Xe dynamic MRS and gas-exchange MRI uniquely provide concurrent, noninvasive assessment of both haemodynamics and gas-exchange impairment that may aid in the detection of PH.

Pulmonary Artery Wave Intensity Analysis in Pulmonary Hypertension Due to Left Heart Disease

<h3>Purpose</h3> Wave intensity analysis (WIA) uses simultaneous changes in the pressure and flow velocity to determine wave energy, type and timing of traveling waves in the circulation. Pulmonary artery WIA has not been studied in patients with heart failure. We hypothesise that WIA can differentiate patients with combined pre- and post-capillary pulmonary hypertension (PH) from isolated post-capillary PH. <h3>Methods</h3> Right heart catheterisation was performed using a balloon floatation catheter. Pressure and velocity data were acquired simultaneously using a dual-tipped pressure and doppler flow sensor wire. The data were processed offline using customised Matlab software. <h3>Results</h3> We studied 20 patients with heart failure [Table]. Eight patients had backward compressions wave (BCW). The representative wave intensity (dI) pattern with pressure (P) and velocity (U) profile is shown in Figure 1. The black line denotes total pressure, velocity and wave intensity, the blue dotted line denotes forward going waves and red dotted lines denotes backward going waves. Figures 1a and 1b show the groups with and without a BCW. Typically a forward compression wave (FCW) in early systole (related to right ventricular systole) is followed by a forward decompression wave (FDW) in diastole. Fig1a shows a BCW immediately following the FCW in systole, which may be indicative of wave reflection in the pulmonary circulation. Patients who displayed a BCW had significantly higher pulmonary artery pressure, TPG, PVR and significantly lower PAC. <h3>Conclusion</h3> The presence of a BCW on pulmonary WIA may identify patients with combined pre- and post-capillary PH.

Reservoir Pressure Analysis in Group 2 Pulmonary Hypertension

<h3>Purpose</h3> The reservoir-wave model, based on the 3-element Windkessel, proposes that the pressure waveform consists of a reservoir pressure (Pres) related to arterial expansion and recoil and a superimposed pressure wave (excess pressure, Pex) generated by forward (ventricular stroke volume and input impedance) and backward travelling waves (related to local arterial properties). In this study we aim to describe Pres in Group 2 isolated post-capillary (IPC) and combined pre and post-capillary (CPC) pulmonary hypertension (PH). <h3>Methods</h3> Pressure and velocity data were acquired simultaneously using a dual-tipped pressure and doppler flow sensor wire during right heart catheterisation. The data were processed offline using customised Matlab software. CPC PH was defined as pulmonary capillary wedge pressure (PCWP) >15mmHg, mean pulmonary arterial pressure (mPAP)>20mmHg and PVR≥3 WU. <h3>Results</h3> Pres but not Pex was higher in CPC compared to IPC PH (Table). A representative pressures and flow tracing is shown in the figure. Higher PA pressures in CPC PH is due to higher Pres secondary to higher PVR, PAC and PCWP. Pres correlated to pulmonary vascular resistance (PVR)(p=0.002;r=0.58),pulmonary capillary wedge pressure(PCWP)(p<0.001;r=0.84) and heart rate(HR)(p=0.01;r=0.487); and negatively correlated to pulmonary artery capacitance(PAC)(p<0.001; r=0.68), but not stroke volume(SV). <h3>Conclusion</h3> This is the first study to compare Pres in group 2 PH. Higher PA pressures in CPC PH is due to higher Pres and not Pex. This suggests input impedance and wave reflection may not be the dominant mechanism in CPC PH.

Pulmonary Hypertension in the Setting of Hemodialysis Arteriovenous Fistulas: Natural History and Outcomes

<h3>Purpose</h3> Patients with arteriovenous fistulas (AVF), whether used for hemodialysis or abandoned prior to or after use, are at increased risk for development of pulmonary hypertension (PH). The purpose of this study is to describe the demographic and clinical characteristics of patients with both arteriovenous fistulas and pulmonary hypertension to better understand this subset of patients. <h3>Methods</h3> All patients ≥18 years old, with echocardiography, AVF placement and/or revision, and right heart catheterization (RHC) procedures seen at the Minneapolis Heart Institute (MHI) between 1/1/2010 and 3/31/2020. Fistula placement must have preceded RHC in order to capture any interactions between the AVF and PH. Patients were grouped by class of PH using standard definitions. <h3>Results</h3> Of 39 patients, one had group 1 PH (pulmonary arterial hypertension, PAH), eight had group 1* PH (combined pre-and post-capillary pulmonary hypertension, CPC-PH), 24 had group 2 PH, two patients had group 3 PH, and four had group 5 PH due to high cardiac output. Hypertension, diabetes, obstructive sleep apnea, and coronary artery disease were the most common comorbidities present. 58% of patients had moderate/severe left atrial enlargement, 49% had moderate/severe right atrial enlargement, and 29% had moderate/severe right ventricular enlargement and dysfunction. Only six patients had a cardiac output greater than 8 L/min, suggesting that high output caused by the fistula was not the primary contributor to most patients' PH. Two-year survival for patients was 56%. <h3>Conclusion</h3> Group 2 PH is predominant among individuals with end-stage renal disease and AVF, suggesting that PH in this population is usually not caused by high flow through AVF, but rather due to comorbidities and other factors. Additionally, low survival estimates suggest that PH is a poor prognostic indicator for patients with ESRD.

Sarcoidosis: Hiding in Plain Sight

<h3>Introduction</h3> Sarcoidosis is a systemic disease that can masquerade as many conditions. Due to its often patchy distribution, myocardial biopsy is only ∼30% sensitive. Herein we present a case of sarcoidosis diagnosed from an extra-cardiac biopsy years after the onset of cardiomyopathy. <h3>Case Report</h3> A 54 year old man initially presented with dyspnea and fatigue due to new onset HFrEF of 20%. He had a significant family history of SCD. His workup revealed non-obstructive CAD, a myxomatous mitral valve with bileaflet prolapse and moderate regurgitation, and a cystic structure attached to the tricuspid valve. Given his frequent ventricular ectopy, he was discharged on guideline therapy for HFrEF and a wearable cardioverter defibrillator. Genetic testing for dilated cardiomyopathies revealed EYA4 and TTN variants of unknown significance. A cardiac MRI a few months later demonstrated no abnormal late gadolinium enhancement and persistent systolic dysfunction, so he underwent AICD implant. His course was further complicated by recurrent admissions for supraventricular and ventricular tachyarrhythmias. A cardiopulmonary exercise stress test demonstrated low-risk results. Further evaluation noted prolonged AV conduction. A RHC revealed mild post-capillary pulmonary hypertension and a mildly decreased cardiac index at 2.01 L/min/m². Months later, he underwent CRT-D upgrade. He started improving functionally until he developed left eyelid swelling, initially thought to be lymphoma. An orbital biopsy revealed non-caseating granulomas. A PET/CT demonstrated FDG uptake within subcarinal lymph nodes but no cardiac uptake. Initially he declined immunomodulatory therapy, but as his symptoms worsened, he started corticosteroids and transitioned to mycophenolate mofetil due to intolerance of methotrexate. Due to disease progression on repeat FDG-PET, he was switched to infliximab. <h3>Summary</h3> The diagnosis of sarcoidosis can be difficult due to its variable presentation, including heart block, heart failure, ventricular arrhythmias and sudden cardiac death. Cardiac involvement occurs in 25% of cases. Our case was complicated by a cMRI that was negative for cardiac involvement, which emphasizes the importance of complimentary inflammatory imaging with FDG-PET. A multidisciplinary approach is needed that engages sarcoid specialists for earlier diagnosis to ensure rapid initiation of therapy to reduce end-organ dysfunction.

Pulmonary Vascular Load Impairs Dynamic Right Ventricular-pulmonary Artery Coupling And Increases Lung Congestion During Exercise In Left Heart Disease

Background Pulmonary hypertension (PH) is common complication of left heart disease (LHD) and associated with poor outcomes. Exertional dyspnea and fatigue are frequently reported symptoms among patients with PH due to LHD, and these symptoms are more severely observed in patients with combined post- and pre-capillary PH (CpcPH) as compared with isolated post-capillary PH (IpcPH). However, the pathophysiologic mechanisms underlying exercise intolerance in this setting remain poorly understood. Methods Subjects with elevated both mean pulmonary artery pressure (>20 mmHg) and pulmonary capillary wedge pressure (PCWP) (>15 mmHg) at rest were classified into two groups: CpcPH (pulmonary vascular resistance [PVR]≥3.0 WU, n=32), IpcPH (PVR<3.0 WU, n=54), and controls (n=52) underwent cardiopulmonary exercise testing with invasive hemodynamics and simultaneous echocardiography and lung ultrasound in a prospective study. Results As compared with controls and IpcPH-LHD, subjects with CpcPH-LHD displayed poorer LV diastolic function, lower left atrial (LA) reservoir and booster strain with greater LA volume and more severe right ventricular systolic dysfunction at rest. With exercise, subjects with CpcPH-LHD displayed more severe exercise-induced pulmonary hypertension, higher right atrial pressure (RAP) and more pronounced right ventricular-pulmonary vascular uncoupling. Peak oxygen consumption was lowest in patients with CpcPH-LHD, coupled with greater limitations in cardiac output reserve and more severe increases in lung congestion, arterial hypoxia and pulmonary vascular resistance (Figure 1). Dynamic ventricular interaction was greatest in CpcPH-LHD, evidenced by greater LV eccentricity index and RAP/PCWP and less increase in LV transmural pressure compared with IpcPH-LHD (Figure 2). Conclusions : Patients with CpcPH-LHD display more severe abnormalities in pulmonary vascular reserve with exercise leading to greater lung congestion and enhanced exertional ventricular interdependence compared to patients with IpcPH-LHD. Further study is required to identify therapies targeting pulmonary vascular disease or ventricular interdependence to improve outcomes in people with CpcPH-LHD. Pulmonary hypertension (PH) is common complication of left heart disease (LHD) and associated with poor outcomes. Exertional dyspnea and fatigue are frequently reported symptoms among patients with PH due to LHD, and these symptoms are more severely observed in patients with combined post- and pre-capillary PH (CpcPH) as compared with isolated post-capillary PH (IpcPH). However, the pathophysiologic mechanisms underlying exercise intolerance in this setting remain poorly understood. Subjects with elevated both mean pulmonary artery pressure (>20 mmHg) and pulmonary capillary wedge pressure (PCWP) (>15 mmHg) at rest were classified into two groups: CpcPH (pulmonary vascular resistance [PVR]≥3.0 WU, n=32), IpcPH (PVR<3.0 WU, n=54), and controls (n=52) underwent cardiopulmonary exercise testing with invasive hemodynamics and simultaneous echocardiography and lung ultrasound in a prospective study. As compared with controls and IpcPH-LHD, subjects with CpcPH-LHD displayed poorer LV diastolic function, lower left atrial (LA) reservoir and booster strain with greater LA volume and more severe right ventricular systolic dysfunction at rest. With exercise, subjects with CpcPH-LHD displayed more severe exercise-induced pulmonary hypertension, higher right atrial pressure (RAP) and more pronounced right ventricular-pulmonary vascular uncoupling. Peak oxygen consumption was lowest in patients with CpcPH-LHD, coupled with greater limitations in cardiac output reserve and more severe increases in lung congestion, arterial hypoxia and pulmonary vascular resistance (Figure 1). Dynamic ventricular interaction was greatest in CpcPH-LHD, evidenced by greater LV eccentricity index and RAP/PCWP and less increase in LV transmural pressure compared with IpcPH-LHD (Figure 2). : Patients with CpcPH-LHD display more severe abnormalities in pulmonary vascular reserve with exercise leading to greater lung congestion and enhanced exertional ventricular interdependence compared to patients with IpcPH-LHD. Further study is required to identify therapies targeting pulmonary vascular disease or ventricular interdependence to improve outcomes in people with CpcPH-LHD.

Prognostic Power of Pulmonary Arterial Compliance Is Boosted by a Hemodynamic Unloading Test With Glyceryl Trinitrate in Heart Failure Patients With Post-capillary Pulmonary Hypertension.

BackgroundPulmonary hypertension (PH) is an established risk factor in patients with heart failure (HF). However, right heart catheterisation (RHC) and vasoreactivity testing (VRT) are not routinely recommended in these patients.MethodsThe primary objective of the present study was to explore the impact of VRT using sublingual glyceryl trinitrate (GTN) on transplant/ventricular assist device-free survival in HF patients with post-capillary PH. RHC parameters were correlated retrospectively with the primary outcome.ResultsThe cohort comprised 154 HF patients with post-capillary PH undergoing RHC with GTN-VRT at a tertiary heart failure centre. Multiple parameters were associated with survival. After adjustment for established prognosis-relevant clinical variables from the MAGGIC Score, variables with the most relevant odds ratios (OR) obtained after GTN-VRT were: calculated effective pulmonary arterial (PA) elastance (adjusted OR 2.26, 95%CI 1.30–3.92; p = 0.004), PA compliance (PAC-GTN; adjusted OR 0.45, 95%CI 0.25–0.80; p = 0.006), and total pulmonary resistance (adjusted OR 2.29, 95%CI 1.34–3.93; p = 0.003). Forest plot analysis including these three variables as well as PAC at baseline, delta PAC, and the presence of combined post- and pre-capillary PH revealed prognostic superiority of PAC-GTN, which was confirmed by Kaplan-Meier analysis.ConclusionsIn our cohort of symptomatic HF patients with post-capillary PH, improved PAC after administration of GTN was associated with survival independent of established hemodynamic and clinical risk factors. VRT using GTN may be better described as unloading test due to GTN's complex effects on the circulation. This could be used for advanced prognostication and should be investigated in further studies.