Association of Left Atrial Appendage Morphology and Function With Stroke and Transient Ischemic Attack in Atrial Fibrillation Patients.

We aimed to correlate left atrial appendage (LAA) structure and function with the history of stroke/transient ischemic attack (TIA) in patients with atrial fibrillation (AF). We analyzed the data of 649 patients with AF who were scheduled for catheter ablation. Patients underwent cardiac computed tomography and transesophageal echocardiography before ablation. The LAA morphologies depicted by cardiac computed tomography were categorized into 4 groups: cauliflower, chicken wing, swan, and windsock shapes. The mean age was 61.3 ± 10.5 years, 33.9% were women. The prevalence of stroke/TIA was 7.1%. After adjustment for the main risk factors, the LAA flow velocity ≤35.3 cm/s (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.09 to 4.61, p = 0.033) and the swan LAA shape (OR 2.69, 95% CI 0.96 to 6.86, p = 0.047) independently associated with a higher risk of stroke/TIA, whereas the windsock LAA morphology proved to be protective (OR 0.32, 95% CI 0.12 to 0.77, p = 0.017) compared with the cauliflower LAA shape. Comparing the differences between the LAA morphology groups, we measured a significantly smaller LAA orifice area (389.3 ± 137.7 mm2 in windsock vs 428.3 ± 158.9 ml in cauliflower, p = 0.021) and LAA volume (7.4 ± 3.0 mm2 in windsock vs 8.5 ± 4.8 mm2 in cauliflower, p = 0.012) in patients with windsock LAA morphology, whereas the LAA flow velocity did not differ significantly. Reduced LAA function and swan LAA morphology were independently associated with a higher prevalence of stroke/TIA, whereas the windsock LAA shape proved to be protective. Comparing the differences between the various LAA morphology types, significantly lower LAA volume and LAA orifice area were measured in the windsock LAA shape than in the cauliflower LAA shape.

Use of a new non-contrast-enhanced BOOST cardiac MR sequence before electrical cardioversion or ablation of atrial fibrillation-a pilot study.

Introduction: Left atrial appendage (LAA) thrombus is the most common source of embolization in atrial fibrillation (AF). Transesophageal echocardiography (TEE) is the gold standard method for LAA thrombus exclusion. Our pilot study aimed to compare the efficacy of a new non-contrast-enhanced cardiac magnetic resonance (CMR) sequence (BOOST) with TEE for the detection of LAA thrombus and to evaluate the usefulness of BOOST images for planning radiofrequency catheter ablation (RFCA) compared with left atrial (LA) contrast-enhanced computed tomography (CT). We also attempted to assess the patients' subjective experiences with TEE and CMR. Methods: Patients with AF undergoing either electrical cardioversion or RFCA were enrolled. Participants underwent pre-procedural TEE and CMR scans to evaluate LAA thrombus status and pulmonary vein anatomy. Patient experiences with TEE and CMR were assessed using a questionnaire developed by our team. Some patients scheduled for RFCA also had pre-procedural LA contrast-enhanced CT. In such cases, the operating physician was asked to subjectively define the quality of the CT and CMR scan on a scale of 1-10 (1 = worst, 10 = best) and comment on CMR's usefulness in RFCA planning. Results: Seventy-one patients were enrolled. In 94.4%, both TEE and CMR excluded, and in 1 patient, both modalities reported the presence of LAA thrombus. In 1 patient, TEE was inconclusive, but CMR excluded LAA thrombus. In 2 patients, CMR could not exclude the presence of thrombus, but in 1 of those cases, TEE was also indecisive. During TEE, 67%, during CMR, only 1.9% of patients reported pain (p < 0.0001), and 89% would prefer CMR in case of a repeat examination. The quality of the left atrial contrast-enhanced CT scans was better compared with the image quality of the CMR BOOST sequence [8 (7-9) vs. 6 (5-7), p < 0.0001]. Still, the CMR images were useful for procedural planning in 91% of cases. Conclusion: The new CMR BOOST sequence provides appropriate image quality for ablation planning. The sequence might be useful for excluding larger LAA thrombi; however, its accuracy in detecting smaller thrombi is limited. Most patients preferred CMR over TEE in this indication.

Predictors and neurological consequences of periprocedural cerebrovascular events following transcatheter aortic valve implantation with self-expanding valves.

Aims: To evaluate the patient- and procedure-related predictors of transcatheter aortic-valve implantation (TAVI)-associated ischemic brain lesions and to assess the effect of silent cerebral ischemic lesions (SCIL) on neurocognitive function. Methods and results: We investigated 113 consecutive patients with severe aortic stenosis who underwent brain magnetic resonance imaging (MRI) within a week following TAVI. To assess periprocedural cerebral ischemic lesions, diffusion-weighted MRI was utilized. We used multivariate linear regression to identify the independent predictors of TAVI-related ischemic lesion volume (ILV) and periprocedural stroke. Neurocognitive evaluation was performed before and following TAVI at 6-month and one-year follow-up. Following TAVI, a total of 944 new cerebral ischemic lesions were detected in 104 patients (92%). The median ILV was 257 µl (interquartile range [IQR]:97.1-718.8µl) with a median lesion number of 6/patient [IQR:2-10]. The majority of ischemic lesions were clinically silent (95%), while 5% of the lesions induced a stroke, which was confirmed by MRI. Predilatation (ß = 1.13[95%CI:0.32-1.93], p = 0.01) and the number of valve positioning attempts during implantation (ß = 0.28[95%CI:0.06-0.50], p = 0.02) increased the log-transformed total ILV. Predilatation (OR = 12.04[95%CI:1.46-99.07], p = 0.02) and alternative access routes (OR = 7.84[95%CI:1.01-61.07], p = 0.02) were associated with stroke after adjustments for comorbidities and periprocedural factors. The presence of SCILs were not associated with a change in neurocognitive function that remained stable during the one-year follow-up. Conclusion: While periprocedural ischemic lesions are frequent, most of them are clinically silent and might not impact the patients' neurocognitive function. The number of valve positioning attempts, predilatation, and alternative access routes should be taken into consideration during TAVI to reduce the ILV and risk for stroke.

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).

Microstructural alterations measured by diffusion tensor imaging following transcatheter aortic valve replacement and their association with cerebral ischemic injury and cognitive function - a prospective study.

PURPOSE: We assessed diffusion tensor imaging (DTI) metric changes of the corpus callosum and cingulum correlated to postprocedural ischemic lesion load (ILL) and cognitive performance in transcatheter aortic valve replacement (TAVR). METHODS: TAVR subjects had DTI post-TAVR (≤ 8 days) and at 6 months (78 participants, males 56%, age 78.8 years ± 6.3) and four neurocognitive tests (pre-TAVR, post-TAVR, 6 months, 1 year). DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were calculated for 7 regions: corpus callosum (genu, body, splenium) and cingulum (cingulate gyrus, parahippocampal cingulum bilaterally). DTI metrics post-TAVR and at 6 months were compared with Student's t-test (p < 0.0071) and ANOVA covarying for sex, ILL (p < 0.05) with post hoc analysis of ILL groups (p < 0.0167). Repeated-measures linear mixed-effect model (p < 0.05) was performed to investigate the effect of time and ILL on cognition. RESULTS: At 6 months, significant decrease of the following DTI metrics was detected: AD (genu, body, splenium, right parahippocampal cingulum: p ≤ 0.0046); MD (body, both cingulate gyri: p ≤ 0.0050); RD (left cingulate gyrus: p = 0.0021); FA (splenium: p < 0.0001). ANOVA confirmed significant effect of female sex on AD + MD reduction (body, right cingulate gyrus) and AD reduction (left cingulate gyrus) (p ≤ 0.0254). Significant negative effect of ILL on some DTI metric changes was found (AD + MD-body: p ≤ 0.0050; MD-left cingulate gyrus: p = 0.0087). Cognitive performance remained stable with significant negative correlation of ILL and retrograde memory and visual scores (p ≤ 0.0483). CONCLUSION: Significant effect of TAVR on cerebral microstructural integrity was found with reduced diffusivities opposite to the trends reported in various neurodegenerative conditions/ageing, notably in women and lower ILL, and with preserved/improved cognition. TRIAL REGISTRATION NUMBER: NCT02826200 at ClinicalTrials.gov; date of registration: 07. July 2016.

Cardiac Amyloidosis with Normal Wall Thickness: Prevalence, Clinical Characteristics and Outcome in a Retrospective Analysis.

Background: Cardiac amyloidosis (CA) is a rare, progressive, infiltrative cardiac disease. Light chain (AL) and transthyretin (ATTR) amyloidosis are in the background in almost all cases. New, easily available diagnostic tools and recently introduced novel therapies for both types of CA put this disease into the field of interest. Increased left ventricular wall thickness (IWT) detected by echocardiography is generally thought to be a necessary part of the diagnosis. We aimed to determine the proportion of CA patients without IWT, and to define the clinical characteristics of this cohort. Methods: In an academic tertiary center for CA, we identified patients diagnosed and treated for CA between January 2009 and February 2022. In a retrospective analysis we defined the proportion of patients with (≥12 mm) and without (<12 mm) IWT, and described their clinical features. Results: We identified 98 patients suitable for the analysis. In total, 70 had AL and 27 ATTR CA; 89 patients had CA with IWT and 9 patients (9%) had CA without IWT. All non-IWT patients had AL type CA. Both group of patients had clinically significant disease, which is supported by the relevant elevation in cardiac biomarker levels. There was no difference between the outcome of the two groups. Conclusion: Patients without IWT form a relevant subgroup among those with CA. Our results suggest that diagnostic algorithms and criteria should take these individuals into consideration, and, therefore, give them access to effective treatments.

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).

Left atrial appendage size is a marker of atrial fibrillation recurrence after radiofrequency catheter ablation in patients with persistent atrial fibrillation.

INTRODUCTION: There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long-term recurrence of AF after catheter ablation, depending on AF type. METHODS: AF patients who underwent point-by-point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence. RESULTS: In total, 561 AF patients (61.9 ± 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 (9.3-43.1) months. Patients with persistent AF had significantly higher body surface area-indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38-3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01-1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF. CONCLUSION: The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF.

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.

Nonlinear optical microscopy is a novel tool for the analysis of cutaneous alterations in pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE, OMIM 264800) is a rare autosomal recessive disorder with ectopic mineralization and fragmentation of elastin fibers. It is caused by mutations of the ABCC6 gene that leads to decreased serum levels of inorganic pyrophosphate (PPi) anti-mineralization factor. The occurrence of severe complications among PXE patients highlights the importance of early diagnosis so that prompt multidisciplinary care can be provided to patients. We aimed to examine dermal connective tissue with nonlinear optical (NLO) techniques, as collagen emits second-harmonic generation (SHG) signal, while elastin can be excited by two-photon excitation fluorescence (TPF). We performed molecular genetic analysis, ophthalmological and cardiovascular assessment, plasma PPi measurement, conventional histopathological examination, and ex vivo SHG and TPF imaging in five patients with PXE and five age- and gender-matched healthy controls. Pathological mutations including one new variant were found in the ABCC6 gene in all PXE patients and their plasma PPi level was significantly lower compared with controls. Degradation and mineralization of elastin fibers and extensive calcium deposition in the mid-dermis was visualized and quantified together with the alterations of the collagen structure in PXE. Our data suggests that NLO provides high-resolution imaging of the specific histopathological features of PXE-affected skin. In vivo NLO may be a promising tool in the assessment of PXE, promoting early diagnosis and follow-up.

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.

Largely Accelerated Arterial Aging in Rheumatoid Arthritis Is Associated With Inflammatory Activity and Smoking in the Early Stage of the Disease.

Background: Rheumatoid arthritis (RA) patients have a shorter life expectancy than the general population primarily due to cardiovascular comorbidities. Objectives: To characterize arterial aging in RA. Patients and Methods: Coronary calcium score (CCS) were available from 112 RA patients; out of these patients, follow-up CCS were measured for 54 randomly selected individuals. Control CCS were obtained from the MESA database (includes 6,000 < participants); arterial age was calculated from CCS. Results: RA patients were significantly older (10.45 ± 18.45 years, p < 0.001) in terms of the arterial age than the age-, gender-, and race-matched controls. The proportion of RA patients who had zero CCS was significantly less (p < 0.01) than that of those in the MESA reference group. Each disease year contributed an extra 0.395 years (p < 0.01) on the top of the normal aging process. However, the rate of the accelerated aging is not uniform, in the first years of the disease it is apparently faster. Smoking (p < 0.05), previous cardiovascular events (p < 0.05), and high blood pressure (p < 0.05) had additional significant effect on the aging process. In the follow-up study, inflammatory disease activity (CRP > 5 mg/L, p < 0.05) especially in smokers and shorter than 10 years of disease duration (p = 0.05) had the largest impact. Conclusion: Arterial aging is faster in RA patients than in control subjects, particularly in the first 10 years of the disease. Inflammation, previous cardiovascular events, and smoking are additional contributing factors to the intensified coronary atherosclerosis progression. These data support that optimal control of inflammation is essential to attenuate the cardiovascular risk in RA.

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.

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.

Three-dimensional dynamic morphology of the mitral valve in different forms of mitral valve prolapse - potential implications for annuloplasty ring selection.

BACKGROUND: Real-time three-dimensional transesophageal echocardiography has increased our understanding of the distinct pathomechanisms underlying functional, ischaemic or degenerative mitral regurgitation. However, potential differences in dynamic morphology between the subtypes of degenerative mitral prolapse have scarcely been investigated. METHODS: In order to compare the dynamic behavior of the different phenotypes of degenerative mitral valve prolapse, real-time three-dimensional transesophageal echocardiography recordings of 77 subjects, 27 with Barlow disease (BD), 32 with Fibroelastic deficiency (FED) and 18 normal controls (NC) were analysed. RESULTS: Geometric annular and valvular parameters of the myxomatous patients were significantly larger compared to controls (BD vs. FED vs. NC 3D annular area: 15 ± 2.8 vs. 13.3 ± 2.4 vs. 10.6 ± 2.3cm(2), all p < 0.01). Beside similar ellipticity, BD annuli were significantly flatter compared to FED. Myxomatous annuli appeared less dynamic than normals, with decreased overall 3D area change, however only the BD group differed from NC significantly (BD vs. FED vs. NC normalized 3D area change 4.40 vs. 6.81 vs. 9.69 %; BD vs. NC p = 0.000; FED vs. NC p = not significant, BD vs. FED p = 0.025). CONCLUSION: BD and FED differ not only in terms of valve morphology, but also annular dynamics. Both pathologies are characterized by annular dilatation. However, in BD the annulus is remarkably flattened and hypodynamic, whereas in FED its saddle-shape and contractile function is relatively preserved. These features might influence the choice of repair technique and the selection of annuloplasty ring.

Arterial-ventricular and interventricular interaction in isolated post-capillary and combined pulmonary hypertension in severe mitral stenosis.

BACKGROUND: Isolated post-capillary pulmonary hypertension (Ipc-PH) is characterized by elevated left atrial pressures that are passively transmitted upstream, whereas combined pre- and post-capillary PH (Cpc-PH) demonstrates additional reactive changes in pulmonary vasculature. The increased load imposed on the right ventricle (RV) influences left ventricular (LV) mechanics by means of interventricular interaction. However, there is lack of evidence to substantiate the effect of possible additional alterations in the arterio-ventricular (AV) coupling and their effect on LV function. Considering the discrepant RV load in Cpc-PH and Ipc-PH, we sought to investigate whether these two conditions are also characterized by differential alterations in AV coupling. METHODS AND RESULTS: Invasive hemodynamic and echocardiographic data of 120 patients with PH due to severe rheumatic mitral stenosis before and immediately after percutaneous valvulotomy, along with 40 age-matched healthy controls, were analyzed. Effective arterial (E a) and ventricular elastance (E es) were measured. PH patients demonstrated elevated LV afterload (E a) along with AV uncoupling, and these derangements were more evident in the Cpc-PH group [E a: 3.3 (2.3-5.4) vs 2.6 (2.1-3.5) mmHg/mL, E a/E es: 0.73 (0.6-0.9) vs 0.88 (0.7-1.2), p < 0.05]. In addition, PH was associated with reduced LV deformation, which was mainly determined by elevated E a, while the effect of interventricular interaction was limited to the septal wall. CONCLUSIONS: Our results suggest that in addition to the interventricular interaction, an abnormal AV coupling contributes to the altered LV mechanics that has been associated with adverse prognosis in Cpc-PH.

Ultrastructure and composition of thrombi in coronary and peripheral artery disease: correlations with clinical and laboratory findings.

INTRODUCTION: Fibrin structure and cellular composition of thrombi profoundly affect the clinical outcomes in ischemic coronary and peripheral artery disease. Our study addressed the interrelations of structural features of thrombi and routinely measured laboratory parameters. MATERIALS AND METHODS: Thrombi removed by thromboaspiration following acute myocardial infarction (n=101) or thrombendarterectomy of peripheral arteries (n=50) were processed by scanning electron microscopy and immunostaining for fibrin and platelet antigen GPIIb/IIIa to determine fibrin fibre diameter and relative occupancy by fibrin and cells. Correlations between the structural characteristics and selected clinical parameters (age, sex, vascular localization, blood cell counts, ECG findings, antiplatelet medication, accompanying diseases, smoking) were assessed. RESULTS: We observed significant differences in mean fibre diameter (122 vs. 135 nm), fibrin content (70.5% vs. 83.9%), fluorescent fibrin/platelet coverage ratio (0.18 vs. 1.06) between coronary and peripheral thrombi. Coronary thrombi from smokers contained more fibrin than non-smokers (78.1% vs. 62.2% mean occupancy). In the initial 24 h, fibrin content of coronary thrombi decreased with time, whereas in peripheral thrombi platelet content increased in the first 7 days. In coronaries, higher platelet content and smaller vessel diameter were associated with thinner fibrin fibres, whereas hematocrit higher than 0.35 correlated with larger intrathrombotic platelet occupancy. Smoking and dyslipidaemia strengthened the dependence of clot platelet content on systemic platelet count (the adjusted determination coefficient increased from 0.33 to 0.43 and 0.65, respectively). CONCLUSION: Easily accessible clinical parameters could be identified as significant determinants of ultrastructure and composition of coronary and peripheral thrombi.

The impact of arterial load on left ventricular performance: an invasive haemodynamic study in severe mitral stenosis.

KEY POINTS: A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading. As most of the methods used to determine LV performance in MS patients are influenced by loading conditions, previous studies have shown conflicting results. The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways. Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness. Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS. ABSTRACT: Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load-independent indices robust to the altered loading state. We studied 106 subjects (32 ± 8 years, 72% female) with severe MS (0.8 ± 0.2 cm(2) ) and 40 age-matched controls. MS subjects underwent simultaneous bi-ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single-beat LV elastance (Ees ) was employed for LV contractility measurements. Effective arterial elastance (Ea ) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea : 3.0 ± 1.3 vs. 1.5 ± 0.3 mmHg ml(-1) ; P < 0.001) and LV contractility (Ees : 4.1 ± 1.6 vs. 2.4 ± 0.5 mmHg ml(-1) ; P < 0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8 cm(2) ) and pronounced subvalvular fusion. Stroke volume (49 ± 16 to 57 ± 17 ml; P < 0.001) and indexed LV end-diastolic volume (LVEDVindex : 57 ± 16 to 64 ± 16 ml m(-2) ; P < 0.001) increased following PTMC while Ees and Ea returned to more normal levels. Elevated LV stiffness was demonstrated at baseline and increased further following PTMC. Our findings provide evidence of elevated LV contractility, increased arterial load and increased diastolic stiffness in severe MS. Following PTMC, both LV contractility and afterload tend to normalize.