Pulmonary Systolic Pressure Research Articles

Evolution over time of cardiac biomarkers, electrocardiographic and echocardiographic features in a large cohort of patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis

Abstract Introduction Data on evolution of transthyretin wild-type cardiac amyloidosis (ATTRwt) during treatment with tafamidis is scarce. This hinders the quest for parameters of response and a priori treatment eligibility. Purpose To study the evolution of biomarkers, ECG, and echocardiographic features during early tafamidis treatment. Methods We prospectively collected data after 12-18 months of treatment in a single-centre database. Changes of NT-proBNP and high-sensitivity Troponin I (hs-cTnI) between baseline and follow-up evaluations (at 12 and 18 months) were tested for significance. For ECG and echocardiographic features, we considered baseline and the last available follow-up (median interval 11.1 months). Results We included 253 patients (median age 77[71-82]years; 90% males). Median (IQR) baseline NT-proBNP was 2472(1355-4749)ng/L, hs-cTnI 47(30-82)ng/L. Furosemide was administered in 58% of cases (median dose 25[25-50]mg/day). Compared to baseline, NT-proBNP was 2342(1316-4148)ng/L at 12 (p=0.886), and 2633(1393-6063)ng/L at 18 months (p=0.285), with 4% and 30% of patients showing ≥30% and ≥300ng/L increase at 12 and 18 months, respectively; hs-cTnI was 46(29-70)ng/L at 12 (p=0.947), and 44(25-68)ng/L at 18 months (p=0.866), with 35% and 7% showing a ≥20% increase at 12 and 18 months, respectively, and 21 (11.5% over 183 analyzable) with increase at 12 and reduction at 18 months. Patients on furosemide were 69% and 70% at 12 and 18 months, respectively; the dose increased to 37.5(25-75)mg/day at 18 months (p=0.009). At baseline, 117(47%) patients had history/permanent atrial fibrillation (AF). Forty-one(16%) had an implantable electronic device, 16(6%) underwent subsequent implantation. Median PR interval was 210(185-240)msec, trending toward prolongation (p=0.054). QRS duration increased (100[86-130]vs120[90-140]msec, p=0.004), together with conduction disturbances (left anterior fascicular block 30[21%]vs43[29%], p=0.036; right bundle branch block 14[10%]vs27[18%], p=0.002). AF prevalence raised from 19% to 25%. There were no significant changes in left ventricular (LV) geometry (septum thickness 18[16-20]vs18[16-20]mm, p=0.666; end-diastolic diameter 45±7vs45±8mm, p=0.434), systolic function (ejection fraction 51±10%vs49±11%, p=0.070), filling pressures (E/e’ 17[11-20]vs14.9[13-19], p=0.086) and left atrial size (mean volume 46±15vs48±13ml/m2, p=0.649). Tricuspid annular plane systolic excursion (18±4vs17±4mm) and pulmonary artery systolic pressure (40[33-45]vs36[30-45]mmHg) remained stable. Conclusions We did not observe neither improvement nor worsening of laboratory/instrumental variables within the first 12-18 months of tafamidis. There was a progression of electrical disorders. After initial progression hs-cTnI tended to improve. Extended follow-up and a matched case-control series will help identify possible later changes useful to monitor treatment response and effects of supporting heart failure treatments.

Prognostic role of right ventricular-pulmonary artery coupling assessed by TAPSE/PASP ratio in patients with heart failure and mildly reduced ejection fraction

Abstract Background The development of right ventricular (RV)-pulmonary arterial (PA) coupling has resulted in a novel and comprehensive index for evaluating RV function in relation to the underlying RV afterload. In patients with heart failure (HF), it is acknowledged that RV-PA uncoupling are features that are associated with poor outcome. The RV-PA coupling index can be readily assessed non-invasively using the ratio of two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). However, few studies have defined the prognostic impact of the TAPSE/PASP ratio in patients with HF and mildly reduced EF (HFmrEF). Methods From the prospective cohort study of 1,410 hospitalized HF patients (age 68+/-15, men 62%) between August 2015 and September 2019, this study enrolled 191 HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41–49%) patients whose TAPSE and PASP were measured during hospitalization and discharged alive. We studied the prognostic impact of TAPSE/PASP ratio on HFmrEF patients using by cut-off value obtained from receiver operating characteristic (ROC) analysis. The primary and secondary endpoints was defined as the all-cause death and HF re-hospitalization after discharge, respectively. Results During median follow-up of 38 [23–52] months, 48 patients (25%) died. The deceased patients had a significantly older (median 75 vs. 71 years, p<0.05), higher rate of ischemic heart disease (50% vs. 23%, p<0.05), elevated brain natriuretic peptide levels (325 vs. 159 pg/ml, p<0.05) and lower rate of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (65% vs. 80%, p<0.05) at discharge. In the ROC analysis, the cut-off value of TAPSE/PASP ratio for mortality was 0.46. Patients with TAPSE/PASP ≤0.46 had a significantly higher all-cause mortality (log-rank p<0.05) and had a tendency of higher rate of HF re-hospitalization than patients with TAPSE/PASP >0.46 (log-rank p=0.06) (Figure). Using multivariate analysis, the lower TAPSE/PASP ratio had an independent predictive value of prognosis in patients with HFmrEF (hazard ratio 2.16, 95% confidence interval; 1.08–3.92, p<0.05) (Table). Conclusion The TAPSE/PASP ratio has a significant prognostic value in patients with HFmrEF. The RV-PA uncoupling assessed by TAPSE/PASP ratio might be useful for risk assessment in patients with HFmrEF.

Right ventricular myocardial work: a step forward for the assessment of right ventricular to pulmonary artery coupling

Abstract Background Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function. By integrating RV global longitudinal strain as systolic function parameter, pulmonary systolic and diastolic pressures as afterload indices, and pulmonary and tricuspid valves timings, RVMW could provide a more comprehensive evaluation of RV function. Purpose The aim of this study was to assess patterns of RVMW indices in patients with preserved and impaired RV to pulmonary artery (PA) coupling (RVAC), as assessed by RV free wall longitudinal strain/pulmonary artery systolic pressure (RVFWLS/PASP) ratio. Methods We studied by echocardiography 158 consecutive patients with stable HF and left ventricular (LV) systolic dysfunction (LV ejection fraction < 50%). RVAC was assessed by RVFWLS/PASP and patients were grouped according to the median value. Four parameters of RVMW were obtained: RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW) and RV global work efficiency (RVGWE). Results According to RVFWLS/PASP ratio, patients were divided into two groups: A) preserved RVAC (RVFWLS/PASP ratio ≥ 0.51; N=84) and B) impaired RVAC (RVFWLS/PASP ratio < 0.51; N= 74). Both RVGWI (371±156 vs 384±207 mmHg%, P=NS) and RVGCW (449±171 vs 516±249 mmHg%, P=NS) did not significantly differ between the two groups (figure 1). However, group B (impaired RVAC) showed significantly greater RV wasted work (94±69 vs 44±30 mmHg%, P=0.0001) and significantly lower RV work efficiency (80±13 vs 88±8 %, P=0.0001) compared to group A (preserved RVAC, figure 2). Conclusions RVMW provided new insight in the RV function assessment, highlighting lower efficiency due to higher wasted work in RV to PA uncoupled patients.Figure 1Figure 2

Assessment of circulating biomarkers and hemodynamic response during stress to detect early cardiopulmonary complications in systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is characterised by persistent immune-inflammatory system activation and excessive extracellular matrix (ECM) accumulation leading to fibrosis. Exercise Doppler Echocardiography (EDE) is a promising method to detect the early changes of fibrosis-related pulmonary and myocardial complications, like elevated left ventricular filling pressure or stress-induced pulmonary hypertension (PH). Aims The study aims to assess the linkage between the activity of fibrosis markers and abnormal exercise haemodynamics during stress in patients with SSc. Methods A total of 18 patients with SSc were enrolled in the single-centre prospective study (age 54±15,5years, 94,4 % women). SSc patients with resting PH and moderate to severe pulmonary fibrosis were excluded. According to a standardised protocol, all subjects underwent resting and exercise echocardiography on a semi-recumbent cycle ergometer with an incremental (25 watts) workload up to the maximally tolerated workload. Measurements focused on the left ventricular diastolic function (E/e’) and right ventricular haemodynamics (estimated systolic pulmonary pressure: PASP, right ventricular coupling: TAPSE/PASP, pulmonary vascular resistance: PVR). Blood samples were taken immediately before the stress test, and the Matrix Metalloproteinase-9 and 2 (MMP-9, MMP-2) levels were assessed with gelatin zymography method. Results During the EDE, PASP from baseline increased significantly (24,6mmHg±11 vs 38±16mmHg, p <0,0001), also PVR (1,2±0,49 vs 1,5±0,15 Wood unit, p<0,001) RV coupling was decreased significantly (1,2±0,68 vs 0,93±0,5, p<0,001). Left ventricular E/e’ was also increased during the stress (8,2±2 vs 10,5±5,1, p<0,05). Enzymatically active MMP-9 level was significantly correlated with RV coupling at rest and stress (p<0,05, r 0,63 at rest and r 0,52 at stress) and negatively correlated with PASP (p<0,05, r:-0,62 at rest and r -0,5 at stress). MMP-2 level only negatively correlated with resting PASP (p<0,05, r:-0,527). The left ventricular parameters did not show any relationship with MMP levels. Conclusions The level of circulating MMP-9 predicts haemodynamic behaviour during stress in SSc. MMPs could be a promising marker for detecting early changes in the right ventricle-pulmonary circulation unit.

Time Interval Between Right Ventricular Early Diastolic Velocity by Tissue and Pulse Wave Doppler: An Index of Right Atrial Pressure in Pulmonary Hypertension Patients

Background: A reversal of time difference between the onset of early diastolic velocity (e’) during tissue Doppler imaging and the onset of mitral inflow (E) has been observed in cases of elevated left atrial pressure. Whether this interval (Te’-E) may be useful to assess right atrial pressure has never been investigated, neither in healthy subjects nor in pulmonary hypertension patients. Methods: Right ventricular Te’-E was assessed in patients with pre-capillary pulmonary hypertension and compared with healthy volunteers who underwent comprehensive echocardiography examination. Te’-E is the difference between the interval from R wave at the superimposed electrocardiogram to the e’ wave during right ventricular tissue Doppler imaging and the interval from the R wave to transtricuspid E wave during pulsed wave Doppler imaging. Right atrial pressure was invasively measured in pulmonary hypertension patients. Results: Fifty-six patients were enrolled. Te’-E was prolonged in pulmonary hypertension subjects compared with healthy subjects (p < 0.001). Amongst the pulmonary hypertension patients, strong correlations were found between Te’-E and right atrial pressure (r = −0.885, p < 0.001), systolic pulmonary pressure (r = −0.85, p < 0.001) and the duration of tricuspid regurgitation (r = 0.72, p < 0.001). The area under the receiver operating characteristic curve of Te’-E in identifying right atrial pressure higher than 15 mm of mercury was 0.992 (sensitivity 100%, specificity 83%). Conclusions: In contrast to the left ventricle, there is a delay in the proto-diastolic filling in pulmonary hypertension patients, which correlates with the increase in systolic pulmonary arterial pressure, right atrial pressure, tricuspid regurgitation duration and restrictive diastolic pattern.

Tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio in chronic thromboembolic pulmonary hypertension improves with balloon pulmonary angioplasty.

Right ventricle (RV)-to-pulmonary artery (PA) coupling measured by the ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) is a meaningful prognostic marker in pulmonary hypertension (PH). It's unclear if balloon pulmonary angioplasty (BPA) treatment of chronic thromboembolic pulmonary hypertension (CTEPH) alters RV-PA coupling measured by TAPSE/PASP. We reviewed CTEPH patients treated with BPA at our institution who had a transthoracic echocardiogram (TTE) before BPA and a follow-up TTE at any point during BPA. TAPSE was obtained from the initial and lattermost TTE; hemodynamics were obtained before each BPA session. Between March 2015 to October 2023, there were 228 patients treated with BPA. After excluding post-PTE patients and those without PH, 67 were included. Initial TAPSE/PASP was 0.39 ± 0.21 mm/mmHg. Using previously defined TAPSE/PASP tertiles in PH (<0.19, 0.19-0.32, >0.32 mm/mmHg), there were 6 patients (9%) in low, 30 (45%) in middle, and 31 (46%) in the high tertiles at baseline. The lower TAPSE/PASP tertiles had more severe baseline hemodynamics (p < 0.001) compared to the high TAPSE/PASP cohort. At follow-up, TAPSE/PASP improved to 0.47 ± 0.20 mm/mmHg (p = 0.023), with 2 (3%), 13 (19%), and 52 (78%) patients in the low, middle, high TAPSE/PASP tertiles, respectively. As patients progress through BPA sessions, the TAPSE/PASP ratio increases, possibly reflecting improved RV mechanics and RV-PA coupling. TAPSE/PASP ratio as a marker of RV-PA coupling can improve with BPA treatment and may be an important measure to follow during treatment of CTEPH.

Nuclear factor of activated T-cells 5 is indispensable for a balanced adaptive transcriptional response of lung endothelial cells to hypoxia.

Chronic hypoxia causes detrimental structural alterations in the lung, which may cause pulmonary hypertension and are partially mediated by the endothelium. While its relevance for the development of hypoxia-associated lung diseases is well known, determinants controlling the initial adaptation of the lung endothelium to hypoxia remain largely unexplored. We revealed that hypoxia activates the transcription factor nuclear factor of activated T-cells 5 (NFAT5) and studied its regulatory function in murine lung endothelial cells (MLECs). EC-specific knockout of Nfat5 (Nfat5(EC)-/-) in mice exposed to normobaric hypoxia (10% O2) for 21 days promoted vascular fibrosis and aggravated the increase in pulmonary right ventricular systolic pressure as well as right ventricular dysfunction as compared with control mice. Microarray- and single-cell RNA-sequencing-based analyses revealed an impaired growth factor-, energy-, and protein-metabolism-associated gene expression in Nfat5-deficient MLEC after exposure to hypoxia for 7 days. Specifically, loss of NFAT5 boosted the expression and release of platelet-derived growth factor B (Pdgfb)-a hypoxia-inducible factor 1 alpha (HIF1α)-regulated driver of vascular smooth muscle cell (VSMC) growth-in capillary MLEC of hypoxia-exposed Nfat5(EC)-/- mice, which was accompanied by intensified VSMC coverage of distal pulmonary arteries. Collectively, our study shows that early and transient subpopulation-specific responses of MLEC to hypoxia may determine the degree of organ dysfunction in later stages. In this context, NFAT5 acts as a protective transcription factor required to rapidly adjust the endothelial transcriptome to cope with hypoxia. Specifically, NFAT5 restricts HIF1α-mediated Pdgfb expression and consequently limits muscularization and resistance of the pulmonary vasculature.

Instantaneous Right Ventricular to Pulmonary Artery Systolic Pressure Difference in Cardiac Surgery: A Retrospective and Prospective Cohort Study

BackgroundDuring cardiac surgery, right ventricular outflow tract obstruction (RVOTO) is defined as an instantaneous pressure difference ≥ 6 mm Hg between right ventricular systolic pressure (RVSP) and pulmonary artery systolic pressure (PASP), for ≥ 5 minutes. Risk factors for RVOTO remain poorly understood. This cohort study was designed to evaluate the incidence, characteristics, and outcomes of the patients who experienced RVOTO. MethodsInstantaneous pressure difference between RVSP and PASP was measured by means of a pulmonary artery catheter with a right ventricular port during cardiac surgery from a retrospective (n = 295) and a prospective (n = 105) cohort. ResultsFrom the retrospective and prospective cohorts, respectively, incidence of RVOTO was 30.2% and 36.2% before cardiopulmonary bypass (CPB) initiation and 43.7% and 47.6% after CPB separation. Before CPB initiation, patients with RVOTO had higher cardiac output (4.2 ± 1.5 vs 3.8 ± 1.1 L/min; P = 0.033) and received more inhaled epoprostenol (79% vs 61%; P = 0.005) and inotropes (66% vs 51%; P = 0.016) compared with those without RVOTO. After CPB separation, patients with RVOTO had higher heart rate (62 ± 15 vs 58 ± 13 beats/min; P = 0.011), cardiac output (4.1 ± 1.4 vs 3.7 ± 1.1 L/min; P = 0.003), and CPB duration (90 ± 45 vs 77 ± 30 min, P = 0.014), had lower fluid balance (758 ± 1123 vs 1063 ± 1089 mL; P = 0.021), and were more exposed to intratracheal milrinone (12% vs 4%; P = 0.015) compared with those without RVOTO. The time with persistent organ dysfunction (TPOD) at 28 days after surgery was similar among patients who had an RVOTO event, before CPB initiation or after CPB separation, compared with those who did not. ConclusionsRVOTO is common in cardiac surgery. However, it is not associated with longer TPOD.

Reappraisal of the Concept and Implications of Pulmonary Hypertension in Degenerative Mitral Regurgitation

BackgroundEuropean and U.S. clinical guidelines diverge regarding pulmonary hypertension (PHTN) in degenerative mitral regurgitation (DMR). Gaps in knowledge underpinning these divergences affect risk assessment and management recommendations attached to systolic pulmonary pressure (SPAP) in DMR. ObjectivesThis study sought to define PHTN links to DMR severity, prognostic thresholds, and independent outcome impact in a large quantitative DMR registry. MethodsThis study gathered a large multicentric registry of consecutive patients with isolated moderate-to-severe DMR, with DMR and SPAP quantified prospectively at diagnosis. ResultsIn 3,712 patients (age 67 ± 15 years, 36% women) with ≥ moderate-to-severe DMR, effective regurgitant orifice (ERO) was 0.42 ± 0.19 cm2, regurgitant volume 66 ± 327 mL/beat and SPAP 41 ± 16 mm Hg. Spline-curve analysis showed excess mortality under medical management emerging around SPAP 35 mm Hg and doubling around SPAP 50 mm Hg. Accordingly, severe pulmonary hypertension (sPHTN) (SPAP ≥50 mm Hg) was detected in 916 patients, moderate pulmonary hypertension (mPHTN) (SPAP 35-49 mm Hg) in 1,128, and no-PHTN (SPAP <35 mm Hg) in 1,668. Whereas SPAP was strongly associated with DMR-ERO, nevertheless excess mortality with sPHTN (adjusted HR: 1.65; 95% CI: 1.24-2.20) and mPHTN (adjusted HR: 1.44; 95% CI: 1.11-1.85; both P ≤ 0.005) was observed independently of ERO and all baseline characteristics and in all patient subsets. Nested models demonstrated incremental prognostic value of mPHTN and sPHTN (all P < 0.0001). Despite higher operative risk with mPHTN and sPHTN, DMR surgical correction was followed by higher survival in all PHTN ranges with strong survival benefit of early surgery (<3 months). Postoperatively, excess mortality was abolished (P ≥ 0.30) in mPHTN, but only abated in sPHTN. ConclusionsThis large international registry, with prospectively quantified DMR and SPAP, demonstrates a Doppler-defined PHTN impact on mortality, independent of DMR severity. Crucially, it defines objectively the new and frequent mPHTN range, independently linked to excess mortality under medical management, which is abolished by DMR correction. Thus, at DMR diagnosis, Doppler-SPAP measurement defining these new PHTN ranges, is crucial to guiding DMR management.

Myocardial performance imaging for the early identification of cardiac dysfunction in neonates with sepsis

PurposeThe assessment of cardiac performance in septic new-borns is crucial for detecting hemodynamic instability and predicting outcome. The aim of the study is to assess myocardial performance in neonates with sepsis for the early identification of cardiac dysfunction.Patients and methodsA case control study was carried out from September 2022 to May 2023 at the Neonatal Intensive care unit, Kasturba Medical College, Manipal. A total of 68 neonates were included in the study, with 33 females and 35 males. The study population was further subdivided into 3 groups namely preterm septic neonates (n = 21), term septic neonates (n = 10) and non-septic healthy controls (n = 37). The cardiac structure and function were assessed using conventional method, Tissue Doppler imaging (Sm) and speckle tracking echocardiography (GLS). The study was approved by the Institutional Ethics Committee at Kasturba Medical College, Manipal (approval number IEC: 90/2022). The CTRI registration number for the study is CTRI/2022/09/045437 and was approved on September 12, 2022. Prior to the neonate’s enrolment, informed consent was obtained from their mothers or legal guardians.ResultsOut of the total 68 neonates, 31 were cases and 37 were controls which included 33 females and 35 males. LV systolic function was not statistically significant between cases and controls. E/A ratio of the mitral valve was significantly lower in septic newborns than in healthy neonates. (1.01 ± 0.35 vs 1.18 ± 0.31, p < 0.05) preterm neonates showed significantly lower Lateral E’ and RV E’ velocities than term neonates. TAPSE was significantly lower in septic preterm neonates. (8.61 ± 1.28 vs. 10.7 ± 2.11, p < 0.05) No significant difference was noted in the Myocardial Performance Index between septic neonates and healthy neonates. LV Global Longitudinal Strain was slightly lower in preterm septic neonates than in term neonates with sepsis.ConclusionSeptic newborns are associated with LV diastolic dysfunction, RV systolic dysfunction and substantially higher pulmonary systolic pressures.

Right Ventriculoarterial Coupling Surrogates and Long-Term Survival in LVAD Recipients: Results of the ASSIST-ICD Multicentric Registry

Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality. The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (P = 0.89), nor was the pulmonary artery pulsatility index (PAPi) (P = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01). Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.

New risk model by right ventricle - pulmonary arterial coupling and inferior vena cava from echocardiography in patients with conventional low-intermediate risk pulmonary artery hypertension under targeted treatment.

Accurately stratifying patients with pulmonary arterial hypertension (PAH) is very important, and traditional risk scores still have internal heterogeneity. This study aimed to construct a risk stratification model that can accurately identify clinical worsening (CW) events in conventional low-intermediate risk patients with pulmonary hypertension under targeted drug treatment by using echocardiographic parameters. This study is a single-center, prospective study, including 105 PAH patients who underwent regular follow-up at Guangdong Provincial People's Hospital from October 2021 to April 2023. The primary endpoint was the occurrence of CW, including death, hospitalization due to pulmonary hypertension, escalation of targeted drug therapy, and worsening of PAH. The predictive value of the echocardiography-based three-strata risk model was assessed using Kaplan-Meier curves and COX regression analysis. A total of 98 PAH patients were ultimately included in this study. The median follow-up duration was 26 months (range 7-28 months). The echocardiography-based three-strata model included the ratio of tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (TAPSE/PASP) and inferior vena cava (IVC). The echocardiography-based three-strata model had higher diagnostic value (C-index=.76) compared to the 2022 ESC/ERS three-strata model and four-strata model (C-index=.66 and C-index=.61, respectively). PAH patients with lower TAPSE/PASP and wider IVC showed a higher CW rate compared to patients with higher TAPSE/PASP and normal IVC (HR=15.1, 95%CI:4.4-51.9, p<.001). The echocardiography-based three-strata model based on TAPSE/PASP and IVC can effectively improve the stratification of low-intermediate risk PAH patients under targeted treatment.

NEW ONSET OF PULMONARY HYPERTENSION IN A PATIENT AFFECTED BY RECURRENT LUNG CANCER

Abstract 39 years old non–smoker female patient came to our observation in July 2023 complaining dyspnea on mild exertion. She had a history of lung adenocarcinoma with epidermal growth factor receptor (EGFR) positive for exon 19 deletion treated with left pneumonectomy and ipsilateral hilar mediastinal lymphadenectomy 5 years earlier, and contralateral disease progression currently treated with chemotherapy. Transthoracic echocardiogram showed circumferential prepericardial effusion requiring pericardiocentesis with transient clinical benefit. Indeed, after a month, she presented with worsening dyspnea and echocardiographic evidence of dilated and hypokinetic right ventricle and severe pulmonary hypertension associated with distal right pulmonary artery stenosis secondary to extrinsic compression by the neoplastic mass as shown by the chest CT scan (fig 1). A right heart catheterization confirmed this finding (minimum diameter of right pulmonary artery of 6 mm, maximum systolic pulmonary blood pressure of 99 mmHg) and a palliative stenting of the distal portion of the right pulmonary artery was performed with resolution of the stenosis, reduction of the pulmonary gradient (fig 2 and 3) and resolution of the dyspnea.

Long-Term Mortality after Transcatheter Edge-to-Edge Mitral Valve Repair Significantly Decreased over the Last Decade: Comparison between Initial and Current Experience from the MiTra Ulm Registry.

(1) Objective: We aimed to assess whether the candidate profile, the long-term outcomes and the predictors for long-term mortality after transcatheter edge-to-edge mitral valve repair (M-TEER) have changed over the last decade; (2) Methods: Long-term follow-up data (median time of 1202 days) including mortality, MACCE and functional status were available for 677 consecutive patients enrolled in the prospective MiTra Ulm registry from January 2010 to April 2019. The initial 340 patients treated in our institution before January 2016 were compared with the following 337 patients; (3) Results: Patients treated after 2016 showed significantly less ventricular dilatation (left ventricular end-systolic diameter of 43 ± 13 mm vs. 49 ± 16 mm, p < 0.007), lower systolic pulmonary pressures (50 ± 15 mmHg vs. 57 ± 21 mmHg, p = 0.01) and a lower prevalence of severe tricuspid regurgitation (27.2% vs. 47.3%, p < 0.001) at baseline than patients treated before 2016. Compared to the cohort treated before 2016, patients treated afterwards showed a significantly lower all-cause 3-year mortality (29.4% vs. 43.8%, p < 0.001) and lower MACCE (38.6% vs. 54.1%, p < 0.001), without differences for MR etiology. While severe tricuspid regurgitation and NYHA class IV remained independently associated with an increased long-term mortality over the last decade, severe left ventricular dilatation (hazard ratio, HR 2.12, p = 0.047) and severe pulmonary hypertension (HR 2.18, p = 0.047) were predictors of long-term mortality only in patients treated before 2016. (4) Conclusions: The M-TEER candidates are currently treated earlier in the course of disease and benefit significantly in terms of a better long-term survival than patients treated at the beginning of the M-TEER era.

Зв’язок рівня інтерлейкіну-6 з клінічним перебігом гострої тромбоемболії легеневої артерії

The aim – to investigate the possible influence of the level of interleukin-6 (IL-6) on the clinical course and remodeling of the right ventricle (RV) in patients with acute pulmonary embolism (PE).Materials and methods. 56 patients with a diagnosis of acute PE, confirmed by сomputed tomographic pulmonary angiography (CTPA), and in whom the level of IL-6 was determined, were studied. The patients were divided into two groups: 1 group with a normal IL-6 level (less than 5.9 pg/ml), 2 group with an elevated IL-6 level (more than 5.9 pg/ml). Clinical and anamnestic and laboratory-instrumental data were analyzed, statistical analysis of the resulting figures was carried out.Results and discussion. When comparing the groups depending on the level of IL-6, it was found that in group 1, not a single case of high-risk PE was recorded (p=0.052), while there was a significantly higher percentage of moderate-low-risk patients, p&lt;0.05. Patients in group 2 had a higher heart rate (p=0.0006), lower SBP (p=0.04) at admission, and a tendency to increase body mass index (p=0.089). In addition, in group 2, the average levels of leukocytes (p=0.046), d-dimer (p=0.007), CRP (p=0.004) were higher, and the level of lymphocytes (p=0.008) was lower than in group 1, and the trend was determined to an increase in neutrophils (p=0.07) and CPK MB (p=0.89) in the 2nd group. According to the ultrasound data, in group 2 there was more often the detection of thrombosis of the veins of the lower extremities (p=0.003), a significantly larger size of the RV (p=0.02), a tendency to increase the size of the right atrium (RA) and a higher level of systolic pulmonary pressure (p=0.068 ). Analysis of the CTPA showed a greater dilatation of the left LA (p=0.0297) and an increase in the LV/LV index (p=0.0072) in the 2nd group. Correlation analysis revealed an inverse connection with the level of SpO2 (p=0.03) and lymphocytes (p=0.0065), a direct connection with heart rate (p&lt;0.001), the ratio of LV/LV index (p=0.046), with the level of troponin I (p=0.014), D-dimer (p=0.026), leukocytes (p=0.026), neutrophils (0.038) and glucose (0.016), as well as the trend regarding the connection between the IL-6 level and the size of the RV according to echocardiography (p=0.07) and CPK MB level (p=0.086). The data of ROC analysis showed the connection of dilatation of the RV and Il-6 from the level of more than 7.65 pg/ml, with a sensitivity of the indicator of 90 %, specificity of 50 %.Conclusions. An Il-6 level increase is more common in elderly patients, patients with venous thrombosis of the lower extremities, tachycardia, hypotension, and with a greater risk of an adverse course during the hospital period. In 2 groups, a higher level of other markers of inflammation (leukocytes, CRP), larger sizes of the RV, a higher level of pulmonary artery pressure according to echocardiography and values of RV/LV according to CTPA results are observed. A direct connection between IL-6 level and heart rate, troponin level, D-dimer level, LV/LV ratio and inverse connection with saturation and lymphocyte level was established according to correlation analysis. Multivariate regression analysis established an independent connection between the IL-6 level and some laboratory (CPK MB, blood glucose) and echocardiographic parameters (RA, LV ESD, LV EDV, LV ESV, LV EF). The threshold level of Il-6, which is accompanied by dilatation of the RV according to Roc-analysis data, was determined.

Association of pulmonary hypertension with the outcome in patients undergoing edge-to-edge mitral valve repair

ObjectivesThe association of pulmonary hypertension (PH) with the outcome after mitral transcatheter edge-to-edge repair (M-TEER) focusing on the new ESC/ERS guidelines definition for PH.BackgroundPH is frequently found in patients with...

Clinical characteristics of obstructive sleep apnea in patients with heart failure

Aims: To investigate the clinical characteristics of obstructive sleep apnea syndrome in patients with heart failure (HF).&#x0D; Patients and Methods: From 9/2020 to 9/2021, patients with chronic HF (European Society of Cardiology’s criteria) and obstructive sleep apnea (American Academy of Sleep Medicine’s criteria) were enrolled into the study. Clinical examination, blood test, echocardiography, polysomnography, ventilatory polygraphy were performed in all patients.&#x0D; Results: 63 patients were included: 54 male (85.7%), 9 female (14.3%), age 69.57 ± 13.08, BMI 28.63 ± 4.16 kg/m2, neck size &gt;40 cm: 69.3%, 100% male and 88.9% female had waist circumference ≥90 cm, hypertension 78.4%, diabetes 47.6%, HFrEF 12 (18%), HFmrEF 5 (7.9%), HFpEF 46 (73%). 68.3% patients had Epworth ≥10, snoring 92.1%. Compared to patients with apnea-hypopnea index (AHI) &lt;15 and AHI 15-30, patients with AHI&gt;30 had thicker interventricular septum, higher left ventricular mass (LVM) and LVM index, lower e’ velocity, higher E/e’ ratio, higher left atrial volume index, higher systolic artery pulmonary pressure, p&lt;0.05. Multivariate regression showed that age, body mass index, neck size, HbA1C were independent predictors of high AHI, p&lt;0.05.&#x0D; Conclusions: Majority of patients with chronic HF and obstructive sleep apnea were male, old age, overweight/obesity, and had large neck size. Hypertension and diabetes and heart failure with preserved ejection fraction were prevalent. Patients with AHI&gt;30 had higher interventricular septal thickness, higher LVM and LVM index, lower e’ velocity, higher E/e’ ratio, higher left atrial volume index, higher systolic artery pulmonary pressure, p&lt;0.05. Age, body mass index, neck size, HbA1C were independent predictors of high AHI, p&lt;0.05.

Right ventricular-pulmonary artery coupling is an independent risk factor for coronary artery lesions in children with Kawasaki disease.

The recognition ability of right ventricular-pulmonary artery (RV-PA) coupling for coronary artery lesions (CAL) in children with Kawasaki disease (KD) has not been well characterized. This study aimed to determine whether RV-PA coupling is an independent the risk factors for CAL in children with KD. Between October 2021 and August 2023, RV-PA coupling was assessed in 59 KD children using the ratio between echocardiographic tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (PASP). Multivariable logistic regression analysis was used to identify the independent risk factors for CAL among the demographic, clinical, laboratory and echocardiographic data. Twenty-nine of 59 KD children had CAL according to the diagnostic criteria of echocardiography. There were significantly different white blood cell count, C-reactive protein, erythrocyte sedimentation rate, left ventricular ejection fraction, PASP and RV-PA coupling at admission, and significantly different acute/subacute phase ratio of RV-PA coupling between KD children with and without CAL ( P < 0.05). Multivariate logistic regression analysis identified that acute/subacute phase ratio of RV-PA coupling (OR = 26.800; 95% CI, 1.276-562.668; P = 0.034) was an independent risk factor for CAL in children with KD. The area under receiver operating characteristic curve for the acute/subacute phase ratio of RV-PA coupling was 0.715 (95%CI: 0.624 - 0.825) to predict CAL in KD children ( P < 0.05), with a sensitivity of 81.25% and a specificity of 62.57% at the optimal cutoff value of 0.839. The acute/subacute phase ratio of RV-PA coupling was an independent risk factor for CAL in KD children.

The Effects of Ketamine-Propofol and Remifentanil-Propofol Combinations on Integrated Pulmonary Index During Sedation in Gastrointestinal System Endoscopy.

Different sedo-analgesia and monitoring methods are used during endoscopic procedures. And yet, there is no consensus on optimal sedating agents. In this study, the main aim is to compare ketamine-propofol and remifentanil propofol sedo-analgesia protocols by monitoring integrated pulmonary index (IPI). The study population is divided into two groups: Group ketamine received 0.25 mg/kg ketamine and 0.75 mg/kg propofol at the beginning of anesthesia. 1 mcg/kg of remifentanil and 0.75 mg/kg propofol were administered to group remifentanil patients at the induction of anesthesia. Anesthesia maintenance was provided by titration of drug doses according to the Ramsey sedation scale. Measurements were taken at four different points in time: just before anesthesia was induced, five minutes after sedation was induced, ten minutes later, and five minutes after the treatment was finished. There was no significant difference in respiratory parameters such as respiratory rate, SPO2, and EtCO2 measured in the T1 time period between the groups. In the T2 time period, a significant difference was found between the groups in the integrated pulmonary index (IPI), sPO2, respiratory rate, and systolic pressure parameters were found to be significantly higher in group ketamine. T3 time period results were higher in these three parameters: IPI, sPO2, and respiration rate. In the T2, T3, T4 time periods, there was a difference between the groups in the respiration count parameter and it was found to be higher in group ketamine. Although it causes slight prolongation in recovery, ketamine is a safe and effective drug that can be used during endoscopic procedures.

ЛЕЧЕНИЕ ЛЕГОЧНОЙ ГИПЕРТЕНЗИИ У ПАЦИЕНТОВ С СЕРПОВИДНОКЛЕТОЧНОЙ АНЕМИЕЙ С ИСПОЛЬЗОВАНИЕМ СИЛДЕНАФИЛА

Pulmonary hypertension is a common complication of sickle cell disease associated with hemolysis, impaired bioavailability of nitric oxide, and high mortality. The aim of the study is to evaluate the safety and efficacy of selective pulmonary vasodilators and antiproliferative drugs in this risk group. Materials and methods. After optimizing sickle cell therapy to stabilize fetal hemoglobin levels, we evaluated the safety and efficacy of sildenafil in 9 patients with sickle cell disease and pulmonary hypertension. Results. Sildenafil therapy (mean duration 6 ± 1 month) reduced estimated pulmonary systolic pressure [50 ± 4-41 ± 3 mmHg; 9 mmHg difference, 95% confidence interval (CI): 0.3-17, P = 0.043] and increased the 6-minute walking distance (384 ± 30 to 462 ± 28 m; 78 m difference, 95% CI: 40-117, P = 0.0012). Transient headaches were observed in two patients and transient eyelid edema in four patients. The three men in the study did not have any episodes of priapism. Two of them received chronic exchange transfusions, and one had erectile dysfunction. Conclusions. Patients with sickle cell disease and pulmonary hypertension have significant limitations in physical activity. Walking for 6 minutes may be a valid endpoint in this population. Sildenafil therapy is safe and improves pulmonary hypertension and physical performance. Additional phase I studies in men with sickle cell disease are needed, followed by a placebo-controlled phase II/III to evaluate the safety and efficacy of sildenafil therapy in patients with sickle cell disease and pulmonary hypertension.