Echocardiographic estimation of pulmonary artery wedge pressure: invasive derivation, validation, and prognostic association beyond diastolic dysfunction grading.

AIMS: Grading of diastolic function can be useful, but indeterminate classifications are common. We aimed to invasively derive and validate a quantitative echocardiographic estimation of pulmonary artery wedge pressure (PAWP) and to compare its prognostic performance to diastolic dysfunction grading. METHODS AND RESULTS: Echocardiographic measures were used to derive an estimated PAWP (ePAWP) using multivariable linear regression in patients undergoing right heart catheterization (RHC). Prognostic associations were analysed in the National Echocardiography Database of Australia (NEDA). In patients who had undergone both RHC and echocardiography within 2 h (n = 90), ePAWP was derived using left atrial volume index, mitral peak early velocity (E), and pulmonary vein systolic velocity (S). In a separate external validation cohort (n = 53, simultaneous echocardiography and RHC), ePAWP showed good agreement with invasive PAWP (mean ± standard deviation difference 0.5 ± 5.0 mmHg) and good diagnostic accuracy for estimating PAWP >15 mmHg [area under the curve (95% confidence interval) 0.94 (0.88-1.00)]. Among patients in NEDA [n = 38,856, median (interquartile range) follow-up 4.8 (2.3-8.0) years, 2756 cardiovascular deaths], ePAWP was associated with cardiovascular death even after adjustment for age, sex, and diastolic dysfunction grading [hazard ratio (HR) 1.08 (1.07-1.09) per mmHg] and provided incremental prognostic information to diastolic dysfunction grading (improved C-statistic from 0.65 to 0.68, P < 0.001). Increased ePAWP was associated with worse prognosis across all grades of diastolic function [HR normal, 1.07 (1.06-1.09); indeterminate, 1.08 (1.07-1.09); abnormal, 1.08 (1.07-1.09), P < 0.001 for all]. CONCLUSION: Echocardiographic ePAWP is an easily acquired continuous variable with good accuracy that associates with prognosis beyond diastolic dysfunction grading.

Longitudinal strain analysis for assessment of early cardiotoxicity during anthracycline treatment in childhood sarcoma: A single center experience.

BACKGROUND: The growing population of long-term childhood cancer survivors encounter a substantial burden of cardiovascular complications. The highest risk of cardiovascular complications is associated with exposure to anthracyclines and chest radiation. Longitudinal cardiovascular surveillance is recommended for childhood cancer patients; however, the optimal methods and timing are yet to be elucidated. AIMS: We aimed to investigate the feasibility of different echocardiographic methods to evaluate left ventricular systolic function in retrospective datasets, including left ventricular ejection fraction (LVEF), fractional shortening (FS), global longitudinal strain (GLS) and longitudinal strain (LS) as well as the incidence and timing of subclinical left ventricular dysfunction detected by these methods. METHODS AND RESULTS: A retrospective longitudinal study was performed with re-analysis of longitudinal echocardiographic data, acquired during treatment and early follow-up, including 41 pediatric sarcoma patients, aged 2.1-17.8 years at diagnosis, treated at Astrid Lindgren Children's Hospital, Stockholm, Sweden, during the period 2010-2021. All patients had received treatment according to protocols including high cumulative doxorubicin equivalent doses (≥250 mg/m2 ). In 68% of all 366 echocardiograms, LS analysis was feasible. Impaired LS values (<17%) was demonstrated in >40%, with concomitant impairment of either LVEF or FS in 20% and combined impairment of both LVEF and FS in <10%. Importantly, there were no cases of abnormal LVEF and FS without concomitant LS impairment. CONCLUSION: Our findings demonstrate feasibility of LS in a majority of echocardiograms and a high incidence of impaired LS during anthracycline treatment for childhood sarcoma. We propose inclusion of LS in pediatric echocardiographic surveillance protocols.

BASILICA Procedure Prior to Valve-in-Valve TAVR in a Supra-Annular TAV Prosthesis.

An 80-year-old man with a supra-annular transcatheter aortic valve (TAV) prosthesis presented with severe transvalvular aortic regurgitation 18 months after the TAV replacement procedure. The authors report the first ever valve-in-valve procedure using BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) in such a supra-annular TAV prosthesis. Minimal paravalvular leakage, normal coronary artery flow, and easy coronary access were seen postimplantation. (Level of Difficulty: Advanced.).

Subclinical leaflet thrombosis after transcatheter aortic valve implantation is associated with silent brain injury on brain magnetic resonance imaging.

AIMS: Whether hypoattenuated leaflet thickening (HALT) following transcatheter aortic valve implantation (TAVI) carries a risk of subclinical brain injury (SBI) is unknown. We investigated whether HALT is associated with SBI detected on magnetic resonance imaging (MRI), and whether post-TAVI SBI impacts the patients' cognition and outcome. METHODS AND RESULTS: We prospectively enrolled 153 patients (age: 78.1 ± 6.3 years; female 44%) who underwent TAVI. Brain MRI was performed shortly post-TAVI and 6 months later to assess the occurrence of acute silent cerebral ischaemic lesions (SCIL) and chronic white matter hyperintensities (WMH). HALT was screened by cardiac computed tomography (CT) angiography (CTA) 6 months post-TAVI. Neurocognitive evaluation was performed before, shortly after and 6 months following TAVI. At 6 months, 115 patients had diagnostic CTA and 10 had HALT. HALT status, baseline, and follow-up MRIs were available in 91 cases. At 6 months, new SCIL was evident in 16%, new WMH in 66%. New WMH was more frequent (100 vs. 62%; P = 0.047) with higher median volume (319 vs. 50 mm3; P = 0.039) among HALT-patients. In uni- and multivariate analysis, HALT was associated with new WMH volume (beta: 0.72; 95%CI: 0.2-1.39; P = 0.009). The patients' cognitive trajectory from pre-TAVI to 6 months showed significant association with the 6-month SCIL volume (beta: -4.69; 95%CI: -9.13 to 0.27; P = 0.038), but was not related to the presence or volume of new WMH. During a 3.1-year follow-up, neither HALT [hazard ratio (HR): 0.86; 95%CI: 0.202-3.687; P = 0.84], nor the related WMH burden (HR: 1.09; 95%CI: 0.701-1.680; P = 0.71) was related with increased mortality. CONCLUSIONS: At 6 months post-TAVI, HALT was linked with greater WMH burden, but did not carry an increased risk of cognitive decline or mortality over a 3.1-year follow-up (NCT02826200).

The Predictive Value of Left Atrial Strain Following Transcatheter Aortic Valve Implantation on Anatomical and Functional Reverse Remodeling in a Multi-Modality Study.

Introduction: Transcatheter aortic valve implantation (TAVI) can improve left ventricular (LV) mechanics and survival. Data on the predictive value of left atrial (LA) strain following TAVI are scarce. We aimed to evaluate the association of LA strain measured shortly post-TAVI with functional and anatomical reverse remodeling of the LA and LV, and its association with mortality. Methods: We prospectively investigated 90 patients who underwent TAVI. Transthoracic echocardiography including strain analysis was performed shortly after TAVI and repeated 6 months later. CT angiography (CTA) was performed for pre-TAVI planning and 6 months post-TAVI. Speckle tracking echocardiography was used to determine LA peak reservoir strain (LASr) and LV global longitudinal strain (LV-GL), LA volume index (LAVi) was measured by TTE. LV mass index (LVMi) was calculated using CTA images. LA reverse remodeling was based on LASr and LAVi changes, whereas LV reverse remodeling was defined as an improvement in LV-GLS or a reduction of LVMi. The association of severely reduced LASr (<20%) at baseline with changes (Δ) in LASr, LAVi, LV-GLS and LVMi were analyzed using linear regression, and Cox proportional hazard model for mortality. Results: Mean LASr and LV-GLS were 17.7 ± 8.4 and -15.3 ± 3.4% at baseline and 20.2 ± 10.2 and -16.6 ± 4.0% at follow-up (p = 0.024 and p < 0.001, respectively). Severely reduced LASr at baseline was associated with more pronounced ΔLASr (ß = 5.24, p = 0.025) and LVMi reduction on follow-up (ß = 5.78, p = 0.036), however, the majority of the patients had <20% LASr on follow-up (44.4%). Also, ΔLASr was associated with ΔLV-GLS (adjusted ß = 2.10, p < 0.001). No significant difference in survival was found between patients with baseline severely reduced LASr (<20%) and higher LASr (≥20%) (p = 0.054). Conclusion: LV reverse remodeling based on LVMi was present even in patients with severely reduced LASr following TAVI, although extensive LA damage based on LA strain was demonstrated by its limited improvement over time. Clinical Trial Registration: (ClinicalTrials.gov number: NCT02826200).

Association between central haemodynamics and renal function in advanced heart failure: a nationwide study from Sweden.

AIMS: Renal dysfunction in patients with heart failure (HF) has traditionally been attributed to declining cardiac output and renal hypoperfusion. However, other central haemodynamic aberrations may contribute to impaired kidney function. This study assessed the relationship between invasive central haemodynamic measurements from right-heart catheterizations and measured glomerular filtration rate (mGFR) in advanced HF. METHODS AND RESULTS: All patients referred for heart transplantation work-up in Sweden between 1988 and 2019 were identified through the Scandiatransplant organ-exchange organization database. Invasive haemodynamic variables and mGFR were retrieved retrospectively. A total of 1001 subjects (49 ± 13 years; 24% female) were eligible for the study. Analysis of covariance adjusted for age, sex, and centre revealed that higher right atrial pressure (RAP) displayed the strongest relationship with impaired GFR [ß coefficient -0.59; 95% confidence interval (CI) -0.69 to -0.48; P < 0.001], followed by lower mean arterial pressure (MAP) (ß coefficient 0.29; 95% CI 0.14-0.37; P < 0.001), and finally reduced cardiac index (ß coefficient 3.51; 95% CI 2.14-4.84; P < 0.003). A combination of high RAP and low MAP was associated with markedly worse mGFR than any other RAP/MAP profile, and high renal perfusion pressure (RPP, MAP minus RAP) was associated with superior renal function irrespective of the degree of cardiac output. CONCLUSIONS: In patients with advanced HF, high RAP contributed more to impaired GFR than low MAP. A higher RPP was more closely related to GFR than was high cardiac index.

Echocardiographic Biventricular Coupling Index to Predict Precapillary Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a frequent and detrimental condition. Right heart catheterization (RHC) is the gold standard to identify PH subtype (precapillary from postcapillary PH) and is key for treatment allocation. In this study, the novel echocardiographic biventricular coupling index (BCI), based on the ratio between right ventricular stroke work index and left ventricular E/E' ratio, was tested for the discrimination of PH subtype using RHC as the comparator. METHODS: BCI was derived in 334 consecutive patients who underwent transthoracic echocardiography and RHC for all indications. BCI was then tested in a validation cohort of 1,349 patients. RESULTS: The accuracy of BCI to identify precapillary PH was high in the derivation cohort (area under the curve, 0.82; 95% CI, 0.78-0.88; P < .001; optimal cut point, 1.9). BCI identified patients with precapillary PH with high accuracy also in the validation cohort (area under the curve, 0.87 [95% CI, 0.85-0.89; P < .001]; subgroup with PH: area under the curve, 0.91 [95% CI, 0.89-0.93; P < .001]; cut point, 1.9; sensitivity, 82%; specificity, 89%; positive predictive value, 77%; negative predictive value, 92%). BCI outperformed both the D'Alto score (Z = 3.56; difference between areas = 0.05; 95% CI, 0.02-0.07; P < .001) and the echocardiographic pulmonary-to-left atrial ratio index (Z = 2.88; difference between areas = 0.02; 95% CI, 0.01-0.04; P = .004). CONCLUSIONS: BCI is a novel, noninvasive index based on routinely available echocardiographic parameters that identifies with high accuracy patients with precapillary PH. BCI may be of value in the screening workup of patients with PH.

The Differential Impact of the Left Atrial Pressure Components on Pulmonary Arterial Compliance-Resistance Relationship in Heart Failure.

BACKGROUND: An increase in the pulmonary capillary wedge pressure (PAWP) has been shown to impact on the inherent relationship between the pulmonary arterial compliance (PAC) and pulmonary vascular resistance (PVR), thus augmenting the pulsatile relative to the resistive load of the right ventricle. However, the PAWP comprises the integration of both the steady and the pulsatile pressure components. We sought to address the differential impact of the these distinct PAWP components on the PAC-PVR relationship in a cohort of patients with heart failure. METHODS AND RESULTS: The study population consisted of 192 patients with hemodynamic findings diagnostic for heart failure. Off-line analysis was performed using the MATLAB software. The steady and pulsatile PAWP components were calculated as mid-A pressure and mean pressure during the V-wave oscillation, respectively. The PAC and PVR were hyperbolically and inversely associated and the subgroup of patients with PAWP above the median (>18 mm Hg) displayed a significant left and downward shift of the curve fit (P < .001). The shift in the PAC-PVR fit between patients with higher versus low steady PAWP was not significant (P = .43). In contrast, there was a significant downward and leftward shift of the PVR-PAC curve fit for the subgroup with a higher pulsatile PAWP (P < .001). Furthermore, only the pulsatile PAWP was significantly associated with the time-constant of the pulmonary circulation, assessed as the PAC × PVR product (P < .001). CONCLUSIONS: In patients with heart failure, the pulsatile rather than the steady PAWP component stands for the previously documented shift of the PAC-PVR relationship occurring at an elevated PAWP.

Critical appraisal of the instantaneous end-diastolic pulmonary arterial wedge pressures.

AIMS: A substantial shift in the field of pulmonary hypertension (PH) is ongoing, as the previous practice of mean pulmonary arterial wedge pressure (PAWPM ) is no longer supported. Instead, aiming for a better estimate of end-diastolic pressures (EDP), instantaneous PAWP at mid-A-wave (PAWPmid-A ) or, in the absence of an A-wave, at 130-160 ms following QRS onset has recently been recommended. Electrocardiogram-gated PAWP (PAWPQRS ) has also been proposed. The quantitative differences as well as the diagnostic and prognostic utility of these novel PAWP measurements have not been evaluated. We set out to address these issues. METHODS AND RESULTS: Pressure tracings of 141 patients with PH due to left heart disease (PH-LHD) and 43 with primary pulmonary arterial hypertension (PAH) were analysed. PAWP was measured as follows: (i) mean pressure (PAWPM ); (ii) per the latest consensus approach [PAWPmid-A , or in atrial fibrillation 130, 140, 150, and 160 ms following QRS onset (PAWP130-160 )]; (iii) at QRS onset (PAWPQRS ); and (iv) Z-point (PAWPZ ). For each PAWP, the corresponding pulmonary vascular resistance (PVR) and diastolic pressure gradient were calculated. The cohort comprised 45% female. Mean age was 66 ± 15. PAWPmid-A was in good agreement with PAWPZ (17.3 [14.5 to 21.2] vs. 17.6 [14.2 to 21.6] mmHg, P = 0.63), whereas PAWPQRS provided significantly lower values (15.3 [12.5 to 19.2] mmHg, P < 0.001). In atrial fibrillation, PAWP130 and PAWPQRS yielded the optimal temporal and quantitative analyses of EDPs. The ability to differentiate PAH from PH-LHD was similar for the various PAWP measurements [PAWPM : area under the curve (AUC) 0.98, confidence interval (CI) 0.96-0.99; PAWPmid-A/130 : AUC 0.94, CI 0.91-0.98; PAWPQRS : AUC 0.96, CI 0.94-0.99, P < 0.001 for all]. PVR based on instantaneous PAWP measurements failed to provide superior prognostic information in PH-LHD as compared with conventional PVR. CONCLUSIONS: Although instantaneous PAWP measurement might better represent EDP, they nevertheless fail to yield incremental diagnostic or prognostic information in PH-LHD as compared with conventional measurements.

Optimizing diastolic pressure gradient assessment.

AIMS: The diastolic pressure gradient (DPG) has been proposed as a marker pulmonary vascular disease in the setting of left heart failure (HF). However, its diagnostic utility is compromised by the high prevalence of physiologically incompatible negative values (DPGNEG) and the contradictory evidence on its prognostic value. Pressure pulsatility impacts on DPG measurements, thus conceivably, pulmonary artery wedge pressure (PAWP) measurements insusceptible to the oscillatory effect of the V-wave might yield a more reliable DPG assessment. We set out to investigate how the instantaneous PAWP at the trough of the Y-descent (PAWPY) influences the prevalence of DPGNEG and the prognostic value of the resultant DPGY. METHODS: Hundred and fifty-three consecutive HF patients referred for right heart catheterisation were enrolled prospectively. DPG, as currently recommended, was calculated. Subsequently, PAWPY was measured and the corresponding DPGY was calculated. RESULTS: DPGY yielded higher values (median, IQR: 3.2, 0.6-5.7 mmHg) than DPG (median, IQR: 0.9, - 1.7-3.8 mmHg); p < 0.001. Conventional DPG was negative in 45% of the patients whereas DPGY in only 15%. During follow-up (22 ± 14 months) 58 patients have undergone heart-transplantation or died. The predictive ability of DPGY ≥ 6 mmHg for the above defined end-point events was significant [HR 2.1; p = 0.007] and independent of resting mean pulmonary artery pressure (PAPM). In contrast, conventional DPG did not comprise significant prognostic value following adjustment for PAPM. CONCLUSION: Instantaneous pressures at the trough of Y-descent yield significantly fewer DPGNEG than conventional DPG and entail superior prognostic value in HF patients with and without PH.

Feasibility and accuracy of tricuspid annular displacement assessed by speckle tracking echocardiography and Doppler tissue imaging.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) is a recommended quantitative measure of right ventricular (RV) longitudinal function assessed by M-mode echocardiography. Offline alternatives are desirable when TAPSE is unavailable. This study aimed to assess the feasibility, reliability, and agreement between retrospectively obtained measures of tricuspid annular displacement using Doppler tissue imaging (TADDTI ) and speckle tracking echocardiography (TADSTE ) compared with reference TAPSE. METHODS: Consecutive subjects referred for evaluation of heart failure were enrolled. Subjects in atrial fibrillation, significant valvular disease, or with poor image quality were excluded. TAPSE was measured during the examination using M-mode. TADSTE was measured as the maximal longitudinal displacement of the RV basal segment in systole using speckle strain imaging. TADDTI was derived offline from color-DTI superimposed grayscale images. RESULTS: 107 subjects (age 60 ± 16; 48% female) were analyzed. Both TADDTI and TADSTE demonstrated good feasibility and excellent intra- and inter-observer concordances. Although both measures demonstrated strong association with TAPSE, TADDTI showcased lower specificity to identify RV dysfunction and higher false positives. Bland-Altman analysis revealed a tendency of TADDTI to underestimate TAPSE (bias = 1.40; SD = 2.74 mm) as compared with TADSTE (bias = 0.27; SD = 2.30mm). Wide limits of agreement were observed for both methods. CONCLUSIONS: TADSTE and TADDTI provide reproducible and feasible quantification of RV function. However, TADDTI significantly underestimates TAPSE limiting the interchangeability of these modalities.

The additive value of echocardiographic pulmonary to left atrial global strain ratio in the diagnosis of pulmonary hypertension.

BACKGROUND: The distinction between pre-capillary and post-capillary pulmonary hypertension (PH) is central to accurate diagnosis and appropriate therapy. We aimed to investigate the ability of the novel echocardiographic pulmonary to left atrial global strain ratio (ePLAGS) to distinguish pre-capillary from post-capillary PH and compare its discriminatory strength with the echocardiographic pulmonary to left atrial ratio (ePLAR). METHODS: Consecutive subjects with unexplained dyspnea or heart failure underwent echocardiography immediately followed by right heart catheterization. Subjects who did not satisfy the ESC/ERS criteria for PH, in atrial fibrillation or under pacemaker therapy, or with significant concomitant valvular disease were excluded. ePLAGS was calculated as peak tricuspid regurgitation velocity divided by left atrial global reservoir strain. RESULTS: One hundred and thirty PH subjects, as defined by right heart catheterization, were included in the analysis (pre-capillary: n = 64, post-capillary: n = 66). ePLAGS was lower in pre-capillary compared with post-capillary PH (0.19 ±â€¯0.14 vs. 0.45 ±â€¯0.58 m/s/%; p = 0.02) and significantly different between combined post- and pre-capillary PH (Cpc-PH) and isolated post-capillary PH (Ipc-PH) (0.62 ±â€¯0.85 vs. 0.32 ±â€¯0.19 m/s/%; p = 0.04). ePLAR was higher in pre-capillary as compared with post-capillary PH (0.37 ±â€¯0.16 vs. 0.20 ±â€¯0.08; p < 0.001) but did not differ between Ipc-PH and Cpc-PH. ePLAGS demonstrated stronger discriminating power than ePLAR to distinguish pre-capillary from post-capillary PH (AUC = 0.80 vs. 0.70). In the setting of post capillary PH, ePLAGS showed reasonable ability to distinguish Ipc-PH from Cpc-PH (AUC = 0.65). ePLAR, however, did not differentiate these two groups (AUC = 0.49; p > 0.05). CONCLUSIONS: ePLAGS accurately differentiates pre-capillary from post-capillary PH and demonstrates higher diagnostic ability than ePLAR.

Doppler estimates of pulmonary vascular resistance to phenotype pulmonary hypertension in heart failure.

An accurate distinction between isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post- and pre-capillary pulmonary hypertension (Cpc-PH) is integral to therapy and prognosis in heart failure (HF). This study aimed to compare the ability of four previously validated Doppler estimates of pulmonary vascular resistance (PVRDoppler) to distinguish Ipc-PH from Cpc-PH in a well-defined HF population. Consecutive subjects referred for HF assessment underwent standard echocardiography immediately followed by right heart catheterization (RHC). Subjects with atrial fibrillation, acute coronary syndrome, significant valvular disease or poor image quality were excluded. PVRDoppler estimates were correlated with invasive PVR and agreement was studied using Bland-Altman analysis. Receiver operating characteristics analyses were performed to determine the ability of PVRDoppler methods to identify PVR > 3WU. 55 HF subjects (58 ± 16 years, 55% Ipc-PH) were analyzed. PVRDoppler estimates demonstrated weak to modest associations with invasive PVR. The Doppler method proposed by Abbas et al. demonstrated relatively strong discriminatory ability to distinguish Ipc-PH from Cpc-PH (AUC = 0.79; 95% CI 0.63-0.96; p = 0.001). However, Bland-Altman analysis revealed wide limits of agreement (bias = 0; SD = 1.83WU) and greater variability at higher mean PVR. Conclusions: PVRDoppler estimates demonstrate reasonable ability to distinguish Ipc-PH from Cpc-PH but may not be reliable independent PH distinguishers in HF.

Left atrial strain improves estimation of filling pressures in heart failure: a simultaneous echocardiographic and invasive haemodynamic study.

AIMS: Left ventricular diastolic pressure estimation is essential for characterization of heart failure (HF). Patients with normal resting left atrial (LA) pressures (LAP), but steep LAP elevation on exertion, pose a particular diagnostic challenge. Current recommendations on echocardiographic LAP estimation have limited accuracy. Our aim was to investigate whether LA mechanical alterations assessed by LA strain (LA-GS) can contribute to non-invasive LAP diagnostics. METHODS AND RESULTS: Simultaneous echocardiographic and right heart catheterization (RHC) data at rest and during exercise was analyzed in 164 prospectively enrolled patients, referred for RHC due to HF symptoms. 56% had preserved ejection fraction (pEF). At rest, 97 patients displayed elevated mean pulmonary arterial wedge pressure (PAWPM); further 32 patients had normal resting, but elevated PAWPM during exercise. LA-GS demonstrated a stronger relationship with resting PAWPM (r = - 0.61, p < 0.001) than any of the indices (E/e', LAVi, TRVmax) incorporated in the currently recommended diagnostic algorithm. The diagnostic ability of LA-GS for detecting elevated resting PAWPM (AUC: 0.80, p < 0.001) outperformed that of the recommended algorithm (AUC: 0.69). Importantly, resting LA-GS performed even better in identifying patients with pathological PAWPM either at rest or during stress (AUC: 0.90, p < 0.001), whereas the diagnostic potential of the current algorithm was modest and limited to pEF patients (AUC = 0.72). Finally, among the non-invasive indices, LA-GS entailed the strongest prognostic value for death or heart transplantation (OR: 2.7; p < 0.05). CONCLUSION: LA-GS comprises a robust method for PAWPM assessment at rest. More importantly, it reliably discerns pathological PAWPM rise on exertion despite normal resting pressures.

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure.

AIMS: Levosimendan improves haemodynamics in acute decompensated heart failure (HF). However, it is increasingly used for repetitive or intermittent infusions in advanced but stable chronic HF, without clear indication, selection criteria, or effect. We tested the hypotheses that (1) levosimendan improves haemodynamics in stable chronic HF and (2) that the response is dependent on baseline clinical and haemodynamic factors. METHODS AND RESULTS: Twenty-three patients [median age 56 (49-64) years, four (17%) women] with stable New York Heart Association (NYHA) III and IV HF received a single 24 h levosimendan infusion. Non-invasive haemodynamics (inert gas re-breathing technique), estimated glomerular filtration rate, and N-terminal pro-brain natriuretic peptide were assessed before and after infusion. Levosimendan had the following effects (median change): a significant increase in cardiac output (+9.8 ± 21.6%; P = 0.026) and decrease in N-terminal pro-brain natriuretic peptide (-28.1 ± 16.3%, P < 0.001), estimated total peripheral resistance (-16.9 ± 18.3%, P = 0.005), and mean arterial pressure (-5.9 ± 8.2%, P = 0.007), but no change in estimated glomerular filtration rate (+0.89 ± 14.0%, P = 0.955). There were no significant associations between baseline clinical and/or haemodynamic factors and the levosimendan effect on cardiac output. CONCLUSIONS: Levosimendan was associated with improved haemodynamics in patients with stable chronic HF, but we could not identify any predictors of the magnitude of haemodynamic response.

Heart rate and dyssynchrony in patients with cardiac resynchronization therapy: a pilot study.

OBJECTIVES: The objective of this pilot study was to describe the impact of paced heart rate on left ventricular (LV) mechanical dyssynchrony in synchronous compared to dyssynchronous pacing modes in patients with heart failure. METHODS: Echocardiography was performed in 14 cardiac resynchronization therapy (CRT) patients at paced heart rates of 70 and 90 bpm in synchronous- (CRT), and dyssynchronous (atrial pacing + wide QRS activation) pacing modes. LV dyssynchrony was quantified using the 12-segment standard deviation model (Ts-SD) derived from Tissue Doppler Imaging. In addition, cardiac cycle intervals were assessed using cardiac state diagrams and stroke volume (SV) and filling pressure were estimated. RESULTS: Ts-SD decreased significantly with CRT at 90 bpm (25 ± 12 ms) compared to 70 bpm (35 ± 15 ms, p = .01), but remained unchanged with atrial pacing at different paced heart rates (p = .96). The paced heart rate dependent reduction in Ts-SD was consistent when Ts-SD was indexed to average Ts and systolic time interval. Cardiac state diagram derived analysis of cardiac cycle intervals demonstrated a significant reduction of the pre-ejection interval and an increase in diastole with CRT compared to atrial pacing. SV was maintained at the higher paced heart rate with CRT pacing but decreased with atrial pacing. DISCUSSION: Due to the small sample size in this pilot study general and firm conclusions are difficult to render. However, the data suggest that pacing at higher heart rates acutely reduces remaining LV dyssynchrony during CRT, but not during atrial pacing with dyssynchronous ventricular activation. These results need confirmation in a larger patient cohort.

Determinants and prognostic implications of the negative diastolic pulmonary pressure gradient in patients with pulmonary hypertension due to left heart disease.

AIMS: The diastolic pulmonary pressure gradient (DPG) has recently been introduced as a specific marker of combined pre-capillary pulmonary hypertension (Cpc-PH) in left heart disease (LHD). However, its diagnostic and prognostic superiority compared with traditional haemodynamic indices has been challenged lately. Current recommendations explicitly denote that in the normal heart, DPG values are greater than zero, with DPG ≥7 mmHg indicating Cpc-PH. However, clinicians are perplexed by the frequent observation of DPG <0 mmHg (DPGNEG ), as its physiological explanation and clinical impact are unclear to date. We hypothesized that large V-waves in the pulmonary artery wedge pressure (PAWP) curve yielding asymmetric pressure transmission might account for DPGNEG and undertook this study to clarify the physiological and prognostic implications of DPGNEG . METHODS AND RESULTS: Right heart catheterization and echocardiography were performed in 316 patients with LHD due to primary myocardial dysfunction or valvular disease. A total of 256 patients had PH-LHD, of whom 48% demonstrated DPGNEG . The V-wave amplitude inversely correlated with DPG (r = -0.45, P < 0.001) in patients with low pulmonary vascular resistance (PVR), but not in those with elevated PVR (P > 0.05). Patients with large V-waves had negative and lower DPG than those without augmented V-waves (P < 0.001) despite similar PVR (P >0.05). Positive, but normal DPG (0-6 mmHg) carried a worse 2-year prognosis for death and/or heart transplantation than DPGNEG (hazard ratio 2.97; P < 0.05). CONCLUSION: Our results advocate against DPGNEG constituting a measurement error. We propose that DPGNEG can partially be ascribed to large V-waves and carries a better prognosis than DPG within the normal positive range.