Clinical Characteristics and Outcomes Associated With Distinct Hemodynamic Patterns in End-stage Liver Disease: A Retrospective Cohort Analysis.

Introduction: Despite advances in the diagnosis and therapeutics strategies for pulmonary hypertension (PH) in patients with end-stage liver disease (ESLD), the impact of hemodynamic patterns among ESLD patients identified through right heart catheterization (RHC) on clinical outcomes remains poorly understood. Methods: This single-center retrospective cohort study identified patients diagnosed with ESLD who underwent RHC from August 2018 to June 2023. Demographic and clinical data, including comorbidities, transthoracic echocardiography, and RHC findings, were obtained. Our outcomes of interest were all-cause mortality and the chance of receiving orthotopic liver transplantation (OLT) within a year after RHC. Kaplan-Meier with log-rank test was employed to generate survival curves. Results: We identified 415 ESLD patients with the RHC results. The median (IQR) age was 59 years (52-66), and 62% were male. Caucasians accounted for 43%, followed by African Americans (30%). Up to 89% had a diagnosis of portal hypertension. Median MELD-Na score was 30 (19-36). The etiology of ESLD was mainly from alcohol use (55%). Patients were classified based on RHC results as pre-capillary PH (19%), post-capillary PH (28%), and non-PH (53%) groups. Overall, one-year mortality post-RHC was 22%, with no significant difference in mortality regardless of hemodynamic group. However, the pre-capillary PH group was less likely to receive OLT compared to other groups (P < 0.001). Conclusion: We observed no difference in all-cause mortality among hemodynamic groups. However, pre-capillary PH group were less likely to undergo OLT compared to others. Further investigations are necessary to determine how this should be addressed in clinical practice.

Post-capillary pulmonary hypertension in heart failure: impact of current definition in the PH-HF multicentre study.

BACKGROUND AND AIMS: Based on retrospective studies, the 2022 European guidelines changed the definition of post-capillary pulmonary hypertension (pcPH) in heart failure (HF) by lowering the level of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). However, the impact of this definition and its prognostic value has never been evaluated prospectively. METHODS: Stable left HF patients with the need for right heart catheterization were enrolled from 2010 to 2018 and prospectively followed up in this multicentre study. The impact of the successive pcPH definitions on pcPH prevalence and subgroup [i.e. isolated (IpcPH) vs. combined pcPH (CpcPH)] was evaluated. Multivariable Cox regression analysis was used to assess the prognostic value of mPAP and PVR on all-cause death or hospitalization for HF (primary outcome). RESULTS: Included were 662 HF patients were (median age 63 years, 60% male). Lowering mPAP from 25 to 20 mmHg resulted in +10% increase in pcPH prevalence, whereas lowering PVR from 3 to 2 resulted in +60% increase in CpcPH prevalence (with significant net reclassification improvement for the primary outcome). In multivariable analysis, both mPAP and PVR remained associated with the primary outcome [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00-1.03, P = .01; HR 1.07, 95% CI 1.00-1.14, P = .03]. The best PVR threshold associated with the primary outcome was around 2.2 WU. Using the 2022 definition, pcPH patients had worse survival compared with HF patients without pcPH (log-rank, P = .02) as well as CpcPH compared with IpcPH (log-rank, P = .003). CONCLUSIONS: This study is the first emphasizing the impact of the new pcPH definition on CpcPH prevalence and validating the prognostic value of mPAP > 20 mmHg and PVR > 2 WU among HF patients.

Systemic hemodynamics and pediatric lung disease: mechanistic links and therapeutic relevance.

Chronic lung disease, also known as bronchopulmonary dysplasia, affects thousands of infants worldwide each year. The impact on resources is second only to bronchial asthma, with lung function affected well into adolescence. Diagnostic and therapeutic constructs have almost exclusively focused on pulmonary architecture (alveoli/airways) and pulmonary hypertension. Information on systemic hemodynamics indicates major artery thickness/stiffness, elevated systemic afterload, and/or primary left ventricular dysfunction may play a part in a subset of infants with severe neonatal-pediatric lung disease. Understanding the underlying principles with attendant effectors would aid in identifying the pathophysiological course where systemic afterload reduction with angiotensin-converting enzyme inhibitors could become the preferred treatment strategy over conventional pulmonary artery vasodilatation.NEW & NOTEWORTHY Extremely preterm infants are at a higher risk of developing severe bronchopulmonary dysplasia. In a subset of infants, diuretic and pulmonary vasodilator therapy is ineffective. Recent information points toward systemic hemodynamic disease (systemic arterial stiffness and left ventricular dysfunction) as a contributor via back-pressure changes. Mechanistic links include heightened renin angiotensin aldosterone system activity, inflammation, and oxygen toxicity. Angiotensin-converting enzyme inhibition may be operationally more suited compared with induced pulmonary artery vasodilatation.

The echocardiographic pulmonary to left atrial ratio: A noninvasive variable for the hemodynamic classification of pulmonary hypertension in dogs.

BACKGROUND: Hemodynamic classification of pulmonary hypertension (PH) has important clinical implications. However, only a few echocardiographic variables have been used to hemodynamically classify PH in dogs. OBJECTIVE: To evaluate the echocardiographic pulmonary to left atrial ratio index (ePLAR) in dogs with PH. ANIMALS: Forty-six dogs with intermediate to high probability of PH. METHODS: Cross-sectional study. Variables were compared between dogs with precapillary PH [PrePH (n = 24)] vs postcapillary PH [PostPH (n = 22)], and with combined PH [CombPH (n = 14)] vs isolated PH [IsoPH (n = 8)] using the t-, Mann-Whitney, Pearson's Chi, or Fisher's exact test. The receiver operating characteristic curve and Youden index were used to identify the optimal ePLAR cutoff value to differentiate among the groups, intraclass correlation coefficients (ICC) were used to determine the reliability of measurements. RESULTS: The mean (SD) ePLAR of the PrePH was higher than that of the PostPH group [0.36 (0.13) vs 0.26 (0.09), respectively; P = .005]. The median (interquartile range) ePLAR of the CombPH was higher than that of the IsoPH subgroup [0.29 (0.24-0.38), vs 0.20 (0.16-0.23), respectively; P = .001]. The best cutoff value of ePLAR for identifying IsoPH was <0.245 [AUC at cutoff point = 0.86; sensitivity (95% confidence interval [CI]) = 0.71 (0.47-0.95); specificity (95% CI) = 1 (0.76-1)]. The ICC analysis indicated a high degree of reliability. CONCLUSIONS AND CLINICAL IMPORTANCE: ePLAR can be considered a valid noninvasive variable to hemodynamically classify PH in dogs with an intermediate to high probability of PH. Assessment of ePLAR can be useful in the therapeutic management of PH in dogs.

Nitroprusside Combined with Leg Raise at the Time of Right Heart Catheterization to Differentiate Precapillary from Other Hemodynamic Forms of Pulmonary Hypertension: A Single-Center Pilot Study.

Pulmonary hypertension (PH) can arise from several distinct disease processes, with a percentage presenting with combined pre- and postcapillary pulmonary hypertension (cpcPH). Patients with cpcPH are unsuitable candidates for PH-directed therapies due to elevated pulmonary capillary wedge pressures (PCWPs); however, the PCWP is dynamic and is affected by both preload and afterload. Many patients that are diagnosed with cpcPH are hypertensive at the time of right heart catheterization which has the potential to increase the PCWP and, therefore, mimic a more postcapillary-predominant phenotype. In this small pilot study, we examine the effect of nitroprusside combined with dynamic preload augmentation with a passive leg raise maneuver in hypertensive cpcPH patients at the time of right heart catheterization to identify a more precapillary-dominant PH phenotype. Patients that met the criteria of PCWP ≤ 15 mmHg with nitroprusside infusion and PCWP ≤ 18 mmHg with nitroprusside infusion and simultaneous leg raise were started on pulmonary vascular-targeted therapy. Long-term PH therapy was well tolerated, with increased six-minute walk distance, improved WHO functional class, decreased NT-proBNP, and improved REVEAL 2.0 Lite Risk Score in this precapillary-dominant PH phenotype. This small study highlights the importance of characterizing patient physiology beyond resting conditions at the time of right heart catheterization.

Hemodynamic response to inhaled nitric oxide in patients with pulmonary hypertension and chronic kidney disease: A retrospective cohort study.

Pulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH-CKD) affects approximately 20%-40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH-CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH-CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end-stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface area who underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3 Wood units were included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7% of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc-PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc-PH groups. Among a small subset (n = 14) who were subsequently treated with PAH-targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH-CKD.

A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus.

The recently described perivascular unit (PVU) resides immediately adjacent to the true capillary neurovascular unit (NVU) in the postcapillary venule and contains the normal-benign perivascular spaces (PVS) and pathological enlarged perivascular spaces (EPVS). The PVS are important in that they have recently been identified to be the construct and the conduit responsible for the delivery of metabolic waste from the interstitial fluid to the ventricular cerebrospinal fluid for disposal into the systemic circulation, termed the glymphatic system. Importantly, the outermost boundary of the PVS is lined by protoplasmic perivascular astrocyte endfeet (pvACef) that communicate with regional neurons. As compared to the well-recognized and described neurovascular unit (NVU) and NVU coupling, the PVU is less well understood and remains an emerging concept. The primary focus of this narrative review is to compare the similarities and differences between these two units and discuss each of their structural and functional relationships and how they relate not only to brain homeostasis but also how they may relate to the development of multiple clinical neurological disease states and specifically how they may relate to obesity, metabolic syndrome, and type 2 diabetes mellitus. Additionally, the concept and importance of a perisynaptic astrocyte coupling to the neuronal synapses with pre- and postsynaptic neurons will also be considered as a perisynaptic unit to provide for the creation of the information transfer in the brain via synaptic transmission and brain homeostasis. Multiple electron microscopic images and illustrations will be utilized in order to help explain these complex units.

Post-Capillary Pulmonary Hypertension: Clinical Review.

Pulmonary hypertension (PH) caused by left heart disease, also known as post-capillary PH, is the most common etiology of PH. Left heart disease due to systolic dysfunction or heart failure with preserved ejection fraction, valvular heart disease, and left atrial myopathy due to atrial fibrillation are causes of post-capillary PH. Elevated left-sided filling pressures cause pulmonary venous congestion due to backward transmission of pressures and post-capillary PH. In advanced left-sided heart disease or valvular heart disease, chronic uncontrolled venous congestion may lead to remodeling of the pulmonary arterial system, causing combined pre-capillary and post-capillary PH. The hemodynamic definition of post-capillary PH includes a mean pulmonary arterial pressure > 20 mmHg, pulmonary vascular resistance < 3 Wood units, and pulmonary capillary wedge pressure > 15 mmHg. Echocardiography is important in the identification and management of the underlying cause of post-capillary PH. Management of post-capillary PH is focused on the treatment of the underlying condition. Strategies are geared towards pharmacotherapy and guideline-directed medical therapy for heart failure, surgical or percutaneous management of valvular disorders, and control of modifiable risk factors and comorbid conditions. Referral to centers with advanced heart and pulmonary teams has shown to improve morbidity and mortality. There is emerging interest in the use of targeted agents classically used in pulmonary arterial hypertension, but current data remain limited and conflicting. This review aims to serve as a comprehensive summary of postcapillary PH and its etiologies, pathophysiology, diagnosis, and management, particularly as it pertains to advanced heart failure.

Updates in the Pharmacotherapy of Pulmonary Hypertension in Patients with Heart Failure with Preserved Ejection Fraction.

Pulmonary hypertension (PH) associated with left heart disease (LHD) is a complex cardiopulmonary condition where a variable degree of pulmonary congestion, arterial vasoconstriction and vascular remodeling can lead to PH and right heart strain. Right heart dysfunction has a significant prognostic impact on these patients. Therefore, preserving right ventricular (RV) function is an important treatment goal. However, the treatment of PH in patients with left heart disease has produced conflicting evidence. The transition from pure LHD to LHD with PH is a continuum and clinically challenging. The heart failure with preserved ejection fraction (HFpEF) patient population is heterogeneous when it comes to PH and RV function. Appropriate clinical and hemodynamic phenotyping of patients with HFpEF and concomitant PH is paramount to making the appropriate treatment decision. This manuscript will summarize the current evidence for the use of pulmonary arterial vasodilators in patients with HFpEF.

Precapillary Pulmonary Arterial Hypertension Despite Contrary Anchoring Bias.

We present the case of a patient with risk factors and a noninvasive evaluation that suggested postcapillary pulmonary hypertension, but in fact had invasive hemodynamics consistent with precapillary pulmonary hypertension. A thorough hemodynamic evaluation of pulmonary hypertension must be performed, as treatment is linked to the underlying physiology. (Level of Difficulty: Advanced.).

Can Inhaled Nitric Oxide Response Predict Tolerance to Therapies and Survival in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension?

Inhaled nitric oxide (iNO) relaxes the pulmonary circulation and variably increases the left ventricular preload and pulmonary artery wedge pressure (PAWP)-hemodynamic information that may help guide treatment decisions and assess prognosis in patients with combined precapillary and postcapillary pulmonary hypertension (PH). We included consecutive patients with combined precapillary and postcapillary PH (mean pulmonary artery pressure >20 mm Hg, PAWP >15 mm Hg, and pulmonary vascular resistance [PVR] >2 Woods unit [WU]) who underwent right-sided cardiac catheterization with iNO at the Cleveland Clinic Pulmonary Vascular Disease program between 2017 and 2022. We included 104 patients with baseline PAWP and PVR of 22.2 ± 4.2 mm Hg and 6.1 ± 3.2 WU, respectively. Pulmonary arterial hypertension (PAH) with postcapillary component and PH left heart disease with precapillary component were identified in 27 (26%) and 77 patients (74%), respectively. No side effects were noted during the administration of iNO. During iNO, the PVR decreased 1.1 ± 1.4 WU and the PAWP increased 1.3 ± 3.7 mm Hg. A more pronounced increase in PAWP with iNO was associated with a decrease in PVR (R -0.35, p <0.001) and increase in stroke volume (R 0.20, p = 0.046). Tolerance to PAH-specific medications, overall survival, and heart failure hospitalizations were not significantly associated with the change in PAWP or PVR with iNO. In conclusion, in patients with combined precapillary and postcapillary PH, iNO challenge is safe and caused a significant decrease in PVR, with an increase in PAWP. The changes in PAWP and PVR during iNO administration were not associated with tolerance to PAH-specific medications, heart failure-related hospitalization, or survival.

Diagnosing post-capillary hypertension in patients with left heart disease: impact of new guidelines.

BACKGROUND: In 2022, the definition of pulmonary hypertension (PH) in the presence of left heart disease was updated according to the new joint guidelines of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). The impact of the new ESC/ERS definition on the prevalence of post-capillary PH (pc-PH) and its subgroups of isolated post-capillary (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH) in patients with left heart disease is unclear. METHODS: We retrospectively identified N = 242 patients with left heart disease with available data on right heart catheterisation (RHC) and cardiac magnetic resonance imaging (CMR). The proportion of pc-PH and its subgroups was calculated according to the old and new ESC/ERS PH definition. As the old definition did not allow the exact allocation of all patients with pc-PH into a respective subgroup, unclassifiable patients (Upc-PH) were regarded separately. RESULTS: Seventy-six out of 242 patients had pc-PH according to the new ESC/ERS definitions, with 72 of these patients also meeting the criteria of the old definition. Using the old definition, 50 patients were diagnosed with Ipc-PH, 4 with Cpc-PH, and 18 with Upc-PH. Applying the new definition, Ipc-PH was diagnosed in 35 patients (4 newly), and Cpc-PH in 41 patients. No CMR parameter allowed differentiating between Ipc-PH and Cpc-PH, regardless of which guideline version was used. CONCLUSION: Applying the new ESC/ERS 2022 guideline definitions mildly increased the proportion of patients diagnosed with pc-PH (+ 5.5%) but markedly increased Cpc-PH diagnoses. This effect was driven by the allocation of patients with formerly unclassifiable forms of post-capillary PH to the Cpc-PH subgroup and a significant shift of patients from the Ipc-PH to the Cpc-PH subgroup. Distribution of post-capillary pulmonary hypertension (pc-PH) subgroups according to the European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelines from 2015 and 2022 in N = 242 patients with left heart disease.

3-Year Outcome in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension: Results From PADN-5 Trial.

BACKGROUND: Long-term benefits of pulmonary artery denervation (PADN) for patients with combined precapillary and postcapillary pulmonary hypertension (CpcPH) secondary to left heart failure are unknown. OBJECTIVES: The authors sought to report the 3-year clinical results of PADN for patients with CpcPH. METHODS: A total of 98 patients with CpcPH, defined as having mean pulmonary arterial pressure of ≥25 mm Hg, pulmonary capillary wedge pressure of >15 mm Hg, and pulmonary vascular resistance of >3.0 WU, were randomly assigned to receive the sham + sildenafil or PADN. The primary endpoint was the occurrence of clinical worsening defined as cardiopulmonary death, rehospitalization or heart/lung transplantation at 3-year follow-up. Changes in the 6-minute walk distance and N-terminal pro-B-type natriuretic peptide served as secondary points. RESULTS: At the 3-year follow-up, clinical worsening was reported in 49 (50.0%) patients, with 31 (62.0%) in the sham + sildenafil group and 18 (37.5%) in the PADN group (HR: 2.13 [95% CI: 1.19-3.81]; P = 0.011), largely driven by a higher rate of rehospitalization in the sham + sildenafil group (56.2% vs 35.4%; HR: 1.96 [95% CI: 1.07-3.58]; P = 0.029) by Cox proportional hazards regression. At the end of the study, cardiopulmonary-related deaths occurred in 16 (32.0%) patients in the sham and 9 (18.8%) (P = 0.167) patients in the PADN group. PADN also resulted in a more profound increase in the 6-minute walk distance and reduction in N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: PADN is associated with significant improvements in exercise capacity, cardiac function, and clinical outcomes. Further study without approved drugs for pulmonary arterial hypertension is required to confirm the benefits of PADN for patients with CpcPH. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335).

A normative blood velocity model in the exchange microvessels for discriminating health from disease: Healthy controls versus COVID-19 cases.

A usual practice in medicine is to search for "biomarkers" which are measurable quantities of a normal or abnormal biological process. Biomarkers can be biochemical or physical quantities of the body and although commonly used statistically in clinical settings, it is not usual for them to be connected to basic physiological models or equations. In this work, a normative blood velocity model framework for the exchange microvessels was introduced, combining the velocity-diffusion (V-J) equation and statistics, in order to define the normative range (NR) and normative area (NA) diagrams for discriminating normal (normemic) from abnormal (hyperemic or underemic) states, taking into account the microvessel diameter D. This is different from the usual statistical processing since there is a basis on the well-known physiological principle of the flow diffusion equation. The discriminative power of the average axial velocity model was successfully tested using a group of healthy individuals (Control Group) and a group of post COVID-19 patients (COVID-19 Group).

Corrected MRI Pulmonary Transit Time for Identification of Combined Precapillary and Postcapillary Pulmonary Hypertension in Patients With Left Heart Disease.

BACKGROUND: The identification of combined precapillary and postcapillary pulmonary hypertension (CpcPH) in patients with pulmonary hypertension (PH) due to left heart disease (LHD) can influence therapy and outcome and is currently based on invasively determined hemodynamic parameters. PURPOSE: To investigate the diagnostic value of MRI-derived corrected pulmonary transit time (PTTc) in PH-LHD sub-grouped according to hemodynamic phenotypes. STUDY TYPE: Prospective observational study. POPULATION: A total of 60 patients with PH-LHD (18 with isolated postcapillary PH [IpcPH] and 42 with CpcPH), and 33 healthy subjects. FIELD STRENGTH/SEQUENCE: A 3.0 T/balanced steady-state free precession cine and gradient echo-train echo planar pulse first-pass perfusion. ASSESSMENT: In patients, right heart catheterization (RHC) and MRI were performed within 30 days. Pulmonary vascular resistance (PVR) was used as the diagnostic "reference standard." The PTTc was calculated as the time interval between the peaks of the biventricular signal-intensity/time curve and corrected for heart rate. PTTc was compared between patient groups and healthy subjects and its relationship to PVR assessed. The diagnostic accuracy of PTTc for distinguishing IpcPH and CpcPH was determined. STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, linear and logistic regression analysis, and receiver-operating characteristic curves. Significance level: P < 0.05. RESULTS: PTTc was significantly prolonged in CpcPH compared with IpcPH and normal controls (17.28 ± 7.67 vs. 8.82 ± 2.55 vs. 6.86 ± 2.11 seconds), and in IpcPH compared with normal controls (8.82 ± 2.55 vs. 6.86 ± 2.11 seconds). Prolonged PTTc was significantly associated with increased PVR. Furthermore, PTTc was a significantly independent predictor of CpcPH (odds ratio: 1.395, 95% confidence interval: 1.071-1.816). The area under curve was 0.852 at a cut-off value of 11.61 seconds for PTTc to distinguish between CpcPH and IpcPH (sensitivity 71.43% and specificity 94.12%). DATA CONCLUSION: PTTc may be used to identify CpcPH. Our findings have potential to improve selection for invasive RHC for PH-LHD patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

[2022 ESC/ERS guidelines on the diagnostics and treatment of pulmonary hypertension : A focussed review]. / 2022 ESC/ERS-Leitlinien zur Diagnostik und Therapie der pulmonalen Hypertonie : Ein fokussierter Überblick.

Pulmonary hypertension (PH) is a hemodynamic state that can be caused by a variety of underlying conditions. The pathophysiology is complex and can involve several organ systems, requiring a multidisciplinary approach to differential diagnostics and management. This review article provides a comprehensive overview of the most important changes in the updated 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines on the diagnostics and treatment of pulmonary hypertension, as compared to the previous 2015 version. A special focus is on (i) updated hemodynamic definitions of PH, including general definition, precapillary vs. postcapillary PH, isolated postcapillary PH (IpcPH), combined postcapillary and precapillary PH (CpcPH), (ii) the clinical presentation and classification of PH, (iii) the diagnostic approach as well as (iv) specific aspects of pulmonary arterial hypertension (PAH, group 1), including risk assessment, treatment and PAH with comorbidities, PH associated with left heart (group 2) or lung disease (group 3), and chronic thromboembolic pulmonary hypertension (CTEPH, group 4). Regarding the latter, the specific diagnostic algorithm and the multimodal approach to treatment are presented. Finally, for each of the PH groups, clinically relevant aspects and innovations are briefly and concisely presented.

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

AIMS: 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). METHODS AND RESULTS: 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 (ß = -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. CONCLUSIONS: 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.

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.

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.