Impact of the 2022 pulmonary hypertension definition on haemodynamic classification and mortality in patients with aortic stenosis undergoing valve replacement.

Aims: With the 2022 pulmonary hypertension (PH) definition, the mean pulmonary artery pressure (mPAP) threshold for any PH was lowered from ≥25 to >20 mmHg, and the pulmonary vascular resistance (PVR) value to differentiate between isolated post-capillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH) was reduced from >3 Wood units (WU) to >2 WU. We assessed the impact of this change in the PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR). Methods and results: Severe AS patients (n = 503) undergoing pre-AVR cardiac heart catheterization were classified according to both the 2015 and 2022 definitions. The post-AVR mortality [median follow-up 1348 (interquartile range 948-1885) days] was assessed. According to the 2015 definition, 219 (44% of the entire population) patients had PH: 63 (29%) CpcPH, 125 (57%) IpcPH, and 31 (14%) pre-capillary PH. According to the 2022 definition, 321 (+47%) patients were diagnosed with PH, and 156 patients (31%) were re-classified: 26 patients from no PH to IpcPH, 38 from no PH to pre-capillary PH, 38 from no PH to unclassified PH, 4 from pre-capillary PH to unclassified PH, and 50 from IpcPH to CpcPH (CpcPH: +79%). With both definitions, only the CpcPH patients displayed increased mortality (hazard ratios ≈ 4). Among the PH-defining haemodynamic components, PVR was the strongest predictor of death. Conclusion: In severe AS, the application of the 2022 PH definition results in a substantially higher number of patients with any PH as well as CpcPH. With either definition, CpcPH patients have a significantly increased post-AVR mortality.

Estimated glomerular filtration rate, haemodynamics, and mortality in patients with aortic stenosis.

BACKGROUND: In aortic stenosis (AS), estimated glomerular filtration rate (eGFR) is an important prognostic marker but its haemodynamic determinants are unknown. We investigated the correlation between eGFR and invasive haemodynamics and long-term mortality in AS patients undergoing aortic valve replacement (AVR). METHODS: We studied 503 patients [median (interquartile range) age 76 (69-81) years] with AS [indexed aortic valve area .42 (.33-.49) cm2 /m2 ] undergoing cardiac catheterization prior to surgical (72%) or transcatheter (28%) AVR. Serum creatinine was measured on the day before cardiac catheterization for eGFR calculation (CKD-EPI formula). RESULTS: The median eGFR was 67 (53-82) mL/min/1.73 m2 . There were statistically significant correlations between eGFR and mean right atrial pressure (r = -.13; p = .004), mean pulmonary artery pressure (mPAP; r = -.25; p < .001), mean pulmonary artery wedge pressure (r = -.19; p < .001), pulmonary vascular resistance (r = -.21; p < .001), stroke volume index (r = .16; p < .001), extent of coronary artery disease, and mean transvalvular gradient but not indexed aortic valve area. In multivariate linear regression, higher age, lower haemoglobin, lower mean transvalvular gradient (i.e. lower flow), lower diastolic blood pressure, and higher mPAP were independent predictors of lower eGFR. After a median post-AVR follow-up of 1348 (948-1885) days mortality was more than two-fold higher in patients in the first eGFR quartile compared to those in the other three quartiles [hazard ratio 2.18 (95% confidence interval 1.21-3.94); p = .01]. CONCLUSION: In patients with AS, low eGFR is a marker of an unfavourable haemodynamic constellation as well as important co-morbidities. This may in part explain the association between low eGFR and increased post-AVR mortality.

Systemic blood pressure in severe aortic stenosis: Haemodynamic correlates and long-term prognostic impact.

AIMS: Blood pressure (BP) targets in patients with aortic stenosis (AS) are controversial. This study sought to describe the haemodynamic profile and the clinical outcome of severe AS patients with low versus high central meaarterial pressure (MAP). METHODS AND RESULTS: Patients with severe AS (n = 477) underwent right and left heart catheterization prior to aortic valve replacement (AVR). The population was divided into MAP quartiles. The mean systolic BP, diastolic BP, and MAP in the entire population were 149 ± 25, 68 ± 11, and 98 ± 14 mmHg. Patients in the lowest MAP quartile had the lowest left ventricular ejection fraction (LVEF), systemic vascular resistance, and valvulo-arterial impedance, whereas there were no significant differences in mean right atrial pressure, mean pulmonary artery wedge pressure, pulmonary vascular resistance, and stroke volume index across MAP quartiles. However, left ventricular stroke work index (LVSWI) was lowest in patients in the lowest and highest in those in the highest MAP quartile. After a median (interquartile range) post-AVR follow-up of 3.7 (2.6-5.2) years, mortality was highest in patients in the lowest MAP quartile [hazard ratio 3.08 (95% confidence interval 1.21-7.83); P = 0.02 for lowest versus highest quartile]. In the multivariate analysis, lower MAP [hazard ratio 0.78 (95% confidence interval 0.62-0.99) per 10 mmHg increase; P = 0.04], higher mean right atrial pressure and lower LVEF were independent predictors of death. CONCLUSIONS: In severe AS patients, lower MAP reflects lower systemic vascular resistance and valvulo-arterial impedance, which may help to preserve stroke volume and filling pressures despite reduced left ventricular performance, and lower MAP is a predictor of higher long-term post-AVR mortality.

Long-term follow-up of medically treated patients with spontaneous coronary artery dissection: a prospective, Swiss single-centre cohort study.

AIMS OF THE STUDY: Spontaneous coronary artery dissection (SCAD) is an increasingly diagnosed cause of acute myocardial infarction. However, there is still a limited number of larger cohorts with long-term follow-up. We report on the largest Swiss single-centre cohort to date, with follow-up of up to 22 years. METHODS: We prospectively collected SCAD cases from June 1998 until December 2020. A strategy of systematic follow-up angiography was applied. Information on long-term follow-up was collected up to the end of 2020. Major cardiovascular events (MACE) were defined as all-cause death, non-fatal MI, and non-fatal cardiac arrest. RESULTS: We identified 105 SCAD patients (mean age 53 ± 11 years, 98 female, 5 peripartum). Presentation was myocardial infarction in all patients. In 102 patients, there was one contiguous dissection. Three patients had two (n = 2) or three (n = 1) non-contiguous dissections. In the majority of patients (n = 97), the primary treatment approach was conservative (dual antiplatelet therapy for 12 months in 90% of patients, statins in 91%). Seven patients were treated with percutaneous coronary intervention (PCI) and one patient underwent bypass surgery. Elective follow-up angiograms were performed in 73 asymptomatic patients after a median follow-up of 6.0 months (interquartile range [IQR] 5.5-6.5). These showed healing of the dissection (n = 65) or a good result after PCI (n = 5) in 70 patients. Three patients had a persistent dissection but conservative treatment was continued. After a median follow-up of 7.5 years (IQR 3.6-12.5) (longest follow-up: 22.5 years) there were 15 MACE. Five MACE occurred within 30 days of the index event: death following catastrophic peripartum left main SCAD (n = 1), out-of-hospital cardiac arrest with successful resuscitation 16 days after SCAD (n = 1), ST-segment elevation myocardial infarction due to occlusion of the dissected artery 10 hours after the index angiogram with subsequent PCI (n = 1), SCAD of a second vessel 8 days after the index SCAD (n = 1), and non-ST-segment elevation myocardial infarction with persistent, multisite SCAD 10 days after the index event (n = 1). There were 10 late MACE, including myocardial infarction and recurrent SCAD (different vessel/lesion) a median of 7.6 years (IQR 3.9-9.6) after the index event in eight patients and death with unclear cause in two patients. CONCLUSION: This SCAD series highlights its highly variable clinical course during the acute phase and in the long term. Although most SCAD patients can be treated conservatively with subsequent healing of the dissection and good clinical outcome, there are also patients with dramatic acute presentation or MACE several years after the initial presentation.

Hemodynamics Prior to Valve Replacement for Severe Aortic Stenosis and Pulmonary Hypertension during Long-Term Follow-Up.

(1) Background: Pulmonary hypertension after aortic valve replacement (AVR; post-AVR PH) carries a poor prognosis. We assessed the pre-AVR hemodynamic characteristics of patients with versus without post-AVR PH. (2) Methods: We studied 205 patients (mean age 75 ± 10 years) with severe AS (indexed aortic valve area 0.42 ± 0.12 cm2/m2, left ventricular ejection fraction 58 ± 11%) undergoing right heart catheterization (RHC) prior to surgical (70%) or transcatheter (30%) AVR. Echocardiography to assess post-AVR PH, defined as estimated systolic pulmonary artery pressure > 45 mmHg, was performed after a median follow-up of 15 months. (3) Results: There were 83/205 (40%) patients with pre-AVR PH (defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg by RHC), and 24/205 patients (12%) had post-AVR PH (by echocardiography). Among the patients with post-AVR PH, 21/24 (88%) had already had pre-AVR PH. Despite similar indexed aortic valve area, patients with post-AVR PH had higher mPAP, mean pulmonary artery wedge pressure (mPAWP) and pulmonary vascular resistance (PVR), and lower pulmonary artery capacitance (PAC) than patients without. (4) Conclusions: Patients presenting with PH roughly one year post-AVR already had worse hemodynamic profiles in the pre-AVR RHC compared to those without, being characterized by higher mPAP, mPAWP, and PVR, and lower PAC despite similar AS severity.

Impact of the new pulmonary hypertension definition on long-term mortality in patients with severe aortic stenosis undergoing valve replacement.

BACKGROUND: The new 2018 pulmonary hypertension (PH) definition includes a lower mean pulmonary artery pressure (mPAP) cut-off (>20 mmHg rather than ≥25 mmHg) and the compulsory requirement of a pulmonary vascular resistance (PVR) ≥3 Wood units (WU) to define precapillary PH. We assessed the clinical impact of the 2018 compared to the 2015 PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR). METHODS: Severe AS patients (n = 487) undergoing pre-AVR right heart catheterization were classified according to the 2015 and 2018 definitions. Post-AVR mortality (median follow-up 44 months) was assessed. RESULTS: Based on the 2015 definition, 66 (13%) patients exhibited combined pre and postcapillary PH (CpcPH), 116 (24%) isolated post-capillary PH (IpcPH), 28 (6%) precapillary PH, and 277 (57%) no PH at all. Overall, 52 (11%) patients were reclassified: 23 no PH into IpcPH; 8 no PH into precapillary PH; 20 precapillary PH into no PH; 1 CpcPH into IpcPH. By the 2015 definition, only CpcPH patients displayed increased mortality, whereas by the 2018 definition, precapillary PH patients also experienced higher mortality than those without PH. Among the PH definition components, PVR ≥3 WU was the strongest predictor of death (hazard ratio > 4). CONCLUSIONS: In severe AS, a higher number of IpcPH patients are diagnosed by the 2018 definition, even though they have the same prognosis as those without PH. Patients with true precapillary PH are more accurately identified by the 2018 definition that includes a pulmonary vascular disease criterion, that is, PVR ≥3 WU, a strong mortality predictor.

Wedge Pressure vs Left Ventricular End-Diastolic Pressure for Pulmonary Hypertension Classification and Prognostication in Severe Aortic Stenosis.

BACKGROUND: Differentiation between precapillary and postcapillary pulmonary hypertension (PH) classically relies on mean pulmonary artery wedge pressure (mPAWP). The left ventricular end-diastolic pressure (LVEDP) is proposed as an equivalent alternative. However, mPAWP and LVEDP may differ substantially. We compared the impact of the choice of using the mPAWP vs the LVEDP on PH classification and mortality prediction in patients with severe aortic stenosis (AS) undergoing valve replacement. METHODS: In 335 patients with severe AS , both mPAWP and LVEDP were measured. A mean pulmonary artery pressure ≥ 25 mm Hg was used to define PH, and either mPAWP or LVEDP was used to differentiate between precapillary and postcapillary PH (≤ 15 vs > 15 mm Hg). Mortality after a median follow-up of 1484 days after aortic valve replacement was assessed. RESULTS: Overall, mPAWP was lower than LVEDP (16 ± 8 mm Hg vs 21 ± 8 mm Hg; P < 0.001). Among 140 patients (42%) with PH, the PAWP-based classification revealed 76 (54% of those with PH) with isolated postcapillary PH, 48 (34%) with combined pre- and postcapillary PH, and 16 (12%) with precapillary PH. When the LVEDP was used, 59 patients (42%) were differently classified. These patients had higher mortality than those who were not differently classified [hazard ratio 2.79 (95% confidence interval, 1.17-6.65); P = 0.02]. Higher mPAWP was associated with increased mortality [hazard ratio 1.07 (95% confidence interval, 1.03-1.11) per 1 mm Hg; P = 0.001], whereas higher LVEDP was not. CONCLUSIONS: Use of LVEDP rather than mPAWP results in a divergent PH classification in nearly every second patient with severe AS. These patients have higher mortality after aortic valve replacement. The mPAWP, but not the LVEDP, predicts mortality.

INTRODUCTION: La différentiation entre l'hypertension pulmonaire (HP) précapillaire et postcapillaire repose traditionnellement sur la pression artérielle pulmonaire d'occlusion moyenne (PAPOm). La pression télédiastolique du ventricule gauche (PTDVG) est proposée comme alternative équivalente. Toutefois, la PAPOm et la PTDVG peuvent largement différer. Nous avons comparé les répercussions du choix entre l'utilisation de la PAPOm vs l'utilisation de la PTDVG sur la classification de l'HP et la prédiction de la mortalité des patients atteints d'une sténose aortique (SA) grave qui subissaient un remplacement valvulaire. MÉTHODES: Nous avons mesuré la PAPOm et la PTDVG de 335 patients atteints de SA grave. Nous avons utilisé une pression artérielle pulmonaire moyenne ≥ 25 mmHg pour définir l'HP, et utilisé la PAPOm ou la PTVDG pour différencier entre l'HP précapillaire et postcapillaire (≤ 15 mmHg vs > 15 mmHg). Nous avons évalué la mortalité après un suivi médian de 1 484 jours après le remplacement valvulaire aortique. RÉSULTATS: Dans l'ensemble, la PAPOm était plus faible que la PTVDG (16 ± 8 mmHg vs 21 ±8 mmHg; P < 0,001). Parmi les 140 patients (42 %) atteints d'HP, la classification en fonction de la PAPO a révélé 76 (54 % des patients atteints d'HP) patients atteints d'HP postcapillaire isolée, 48 (34 %) patients atteints d'HP précapillaire et postcapillaire combinée et 16 (12 %) patients atteints d'HP précapillaire. Lorsque nous avons utilisé la PTVDG, 59 patients (42 %) étaient classifiés différemment. La mortalité chez ces patients était plus élevée que chez les patients qui n'étaient pas classifiés différemment (rapport de risque 2,79 [intervalle de confiance à 95 %, 1,17-6,65]; P = 0,02). La PAPOm plus élevée était associée à une mortalité accrue (rapport de risque 1,07 [intervalle de confiance à 95 %, 1,03-1,11] par 1 mmHg; P = 0,001), tandis que la PTVDG plus élevée ne l'était pas. CONCLUSIONS: Le fait d'utiliser la PTVDG plutôt que la PAPOm entraîne une classification divergente de l'HP chez presque tous les deux patients atteints de SA grave. La mortalité après le remplacement valvulaire aortique de ces patients est plus élevée. La PAPOm, mais non la PTVDG, prédit la mortalité.

Impact of a volume challenge on haemodynamics and prognosis in patients with severe aortic stenosis.

AIMS: A volume challenge can unmask pulmonary hypertension (PH) and its mechanism. We evaluated the impact of a volume challenge on mean pulmonary artery pressure (mPAP) and mean pulmonary artery wedge pressure (mPAWP) and its prognostic implications in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). METHODS AND RESULTS: In 285 patients with severe AS (indexed aortic valve area 0.41 ± 0.13 cm2 /m2 ), mPAP and mPAWP were measured before and after administration of 150 ± 58 mL of low-osmolal or iso-osmolal contrast. Following contrast, mPAP and mPAWP rose from 25 ± 10 and 16 ± 8 mmHg by 5 ± 4 and 4 ± 4 mmHg to 30 ± 11 and 20 ± 8 mmHg. There were 112 (39%) patients with pre-contrast PH and 70 (40% of those without pre-contrast PH) patients with post-contrast PH only. Post-contrast PH patients were intermediate between pre-contrast PH and no PH in terms of AS severity, cardiac dysfunction, and haemodynamics. After a median follow-up of 43 months post-AVR, pre-contrast PH patients had numerically the highest mortality driven by those with pre-contrast combined pre-capillary and post-capillary PH (n = 35), while post-contrast changes in mPAP and mPAWP were not related to mortality. Patients with any post-contrast mPAWP > 18 mmHg had significantly higher mortality than those with post-contrast mPAWP ≤ 18 mmHg, CONCLUSIONS: In severe AS, a contrast challenge leads to post-contrast PH in ~40% of patients without pre-contrast PH. However, post-contrast haemodynamic changes do not adversely affect outcomes in patients undergoing AVR. Post-contrast PH represents an intermediate stage of 'cardiac damage', which may be attenuated or reversible after AVR.

Prognostic Usefulness of Cardiac Stress Test Modalities in Patients With Type 2 Diabetes Mellitus Who Underwent Myocardial Perfusion Scintigraphy (from the Basel Asymptomatic High-Risk Diabetics' Outcome Trial).

Our study aimed to assess predictors of the stress test technique used and to evaluate the impact of exercise level achieved on risk stratification in patients with asymptomatic type 2 diabetes without a previous coronary artery disease. Little is known whether co-morbidities of these patients predict the stress technique and whether physical performance provides risk stratification: 400 patients underwent clinical evaluation and myocardial perfusion scintigraphy (MPS) using physical or pharmacological stress. Physical patients were divided into 2 groups: achieving <6 and ≥6 METs, respectively. The mean follow-up time was 2 years. Major cardiac events (MACEs) included myocardial infarction and/or cardiac death. Independent predictors of pharmacological stress were a body mass index of >30 kg/m2 (hazard ratio 1.076, 95% confidence interval 1.027 to 1.127, p = 0.002) and a peripheral arterial disease (hazard ratio 2.888, 95% confidence interval 1.446 to 5.769, p = 0.003). Pharmacological patients had more MACE than physical patients (3.2% vs 1.0%, p = 0.03). Patients achieving <6 METs had a similar MACE rate as pharmacological patients (3.0% vs 3.2%, p = not significant) and more MACE than patients achieving ≥6 METs (3.0% vs 0.4%, p = 0.01). In patients achieving <6 METs and in pharmacological patients, MPS added an incremental prognostic value to pretest information (p values for global chi-square 0.012 and 0.04, respectively). In high-risk asymptomatic diabetic patients, co-morbidities were predictive of the stress technique used. Pharmacological patients had more MACE, similar to those unable to achieve 6 METs. MPS provided an incremental prognostic value in pharmacological patients and in patients with <6METs. In contrast, patients who were able to achieve ≥6 METs were at low risk and do not need further risk stratification.

The outcome of community-acquired pneumonia in patients with chronic lung disease: a case-control study.

BACKGROUND: The impact of chronic lung diseases on outcome in community-acquired pneumonia (CAP) is not well established. We aimed to investigate the outcome of adult CAP-patients with underlying chronic obstructive pulmonary disease (COPD), asthma or interstitial lung disease (ILD) in a case-control study. METHODS: We used a nationwide database including all hospitalisations in Switzerland from 2002 to 2010. Endpoints were the incidence of lung abscess, parapneumonic pleural effusion, empyema, acute respiratory distress syndrome, in-hospital mortality and length of stay. RESULTS: We found less disease-related complications of CAP in COPD (n = 17,075) and asthma (n = 2700) patients compared with their controls. This difference was mainly related to a lower incidence of pleural effusion (COPD: 4.3% vs 4.9%, p = 0.011; asthma: 3.4% vs 5.2%, p <0.001). In-hospital mortality was lower in the COPD and - much more pronounced - asthma cohorts (COPD: 5.8% vs 6.7%, p <0.001; asthma: 1.4% vs 4.8%, p <0.001). For ILD (n = 916), the complication rate was similar as compared to the control group, whereas in-hospital mortality was markedly higher (16.3% vs 6.8%, p <0.001). CONCLUSIONS: These rather unexpected results should be viewed as hypothesis generating, with various possible explanations for our findings. These include the possible influence of inhaled corticosteroid therapy, a possibly higher awareness of general practitioners and hospital physicians while treating patients with chronic lung diseases, a different infective agent spectrum or a different immune response.