Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.

Impact of Cardiac Magnetic Resonance on the Diagnosis of Left Ventricular Noncompaction-A 15-Year Experience.

The aim of this study was to assess the impact of cardiac magnetic resonance (CMR) on the diagnosis in patients with known or suspected left ventricular noncompaction (LVNC). We retrospectively reviewed the medical charts of 12,811 consecutive patients who had CMR studies between 2008 and 2022 in a large tertiary center. We included patients referred for CMR because of known or suspected LVNC. The study sample consisted of 333 patients, 193 (58.0%) male, median age 39.0 (26.8-51.0) years. Among 74 patients fulfilling the echocardiographic LVNC criteria, the diagnosis was confirmed in 54 (73.0%) cases. In 259 patients with ultrasound-based suspicion of LVNC, CMR led to an LVNC diagnosis in 82 (31.7%) patients. In both groups, CMR led to a new diagnosis in 89 cases (10 (13.5%) and 79 (30.5%)). A quantity of 38 (5.4%) patients were diagnosed with dilated cardiomyopathy, 11 (1.4%) patients were diagnosed with hypertrophic cardiomyopathy, and 21 (4.1%) patients were diagnosed with unclassified cardiomyopathy. In four patients with suspected LVNC, a myocardial trabeculation was a secondary result of dilatation due to coronary heart disease. In five cases, valvular heart disease was found. Four patients were diagnosed with athlete's heart. Other diagnoses (arrhythmogenic right ventricular cardiomyopathy, peripartum cardiomyopathy, hypokinetic non-dilated cardiomyopathy, sarcoidosis, amyloidosis, and ventricular septum defect) were found in six patients. CMR is a valuable tool in the evaluation of cardiac muscle and in differentiating LVNC and other cardiac diseases.

The ratio of right ventricular volume to left ventricular volume reflects the impact of pulmonary regurgitation independently of the method of pulmonary regurgitation quantification.

BACKGROUND: Previous studies have advocated quantifying pulmonary regurgitation (PR) by using PR volume (PRV) instead of commonly used PR fraction (PRF). However, physicians are not familiar with the use of PRV in clinical practice. The ratio of right ventricle (RV) volume to left ventricle volume (RV/LV) may better reflect the impact of PR on the heart than RV end-diastolic volume (RVEDV) alone. We aimed to compare the impact of PRV and PRF on RV size expressed as either the RV/LV ratio or RVEDV (mL/m(2)). METHODS: Consecutive patients with repaired tetralogy of Fallot were included (n=53). PRV, PRF and ventricular volumes were measured with the use of cardiac magnetic resonance. RESULTS: RVEDV was more closely correlated with PRV when compared with PRF (r=0.686, p<0.0001, and r=0.430, p=0.0014, respectively). On the other hand, both PRV and PRF showed a good correlation with the RV/LV ratio (r=0.691, p<0.0001, and r=0.685, p<0.0001, respectively). Receiver operating characteristic analysis showed that both measures of PR had similar ability to predict severe RV dilatation when the RV/LV ratio-based criterion was used, namely the RV/LV ratio>2.0 [area under the curve (AUC)(PRV)=0.770 vs AUC(PRF)=0.777, p=0.86]. Conversely, with the use of the RVEDV-based criterion (>170mL/m(2)), PRV proved to be superior over PRF (AUC(PRV)=0.770 vs AUC(PRF)=0.656, p=0.0028]. CONCLUSIONS: PRV and PRF have similar significance as measures of PR when the RV/LV ratio is used instead of RVEDV. The RV/LV ratio is a universal marker of RV dilatation independent of the method of PR quantification applied (PRF vs PRV).

Right ventricular outflow tract obstruction as a confounding factor in the assessment of the impact of pulmonary regurgitation on the right ventricular size and function in patients after repair of tetralogy of Fallot.

PURPOSE: To compare right ventricular (RV) size and function between patients with combined pulmonary regurgitation (PR) plus RV outflow tract (RVOT) obstruction (RVOTO) and patients with isolated PR. MATERIALS AND METHODS: Consecutive individuals with significant PR (PR fraction ≥ 20%) after tetralogy of Fallot (TOF) repair who underwent cardiovascular magnetic resonance (CMR) were included. Patients with additional hemodynamic abnormalities (residual ventricular septal defect, extracardiac shunt, and/or more than mild regurgitation at a valve other than the pulmonary valve) were excluded. Significant RVOTO was defined as peak gradient across RVOT ≥ 30 mmHg. RESULTS: Significant differences between patients with combined PR+RVOTO (n = 9) and isolated PR (n = 33) were observed in RV end-diastolic volume (138.6 ± 25.1 vs. 167.0 ± 34.6 mL/m(2) , P = 0.02, respectively), RV end-systolic volume (65.0 ± 9.6 vs. 92.7 ± 26.2 mL/m(2) , P = 0.003), and RV ejection fraction (RVEF) (52.8 ± 3.7 vs. 45.0 ± 6.4%, P = 0.001). Both PR and peak RVOT gradient were independent predictors of RV size. CONCLUSION: Patients with combined PR+RVOTO had smaller RV volumes and higher RVEF when compared with patients with isolated PR. The confounding effect of RVOTO on RV size and function needs to be considered in CMR studies evaluating patients after TOF repair.

Quantitative assessment of pulmonary regurgitation in patients with and without right ventricular tract obstruction.

BACKGROUND: There are concerns whether there is a difference in clinical utility of pulmonary regurgitation (PR) fraction (PRF) and PR volume (PRV) in subgroups of patients with isolated PR and individuals with combined PR and right ventricular outflow tract obstruction (RVOTO). The aim of the study was to compare PRF and PRV in patients with or without RVOTO. METHODS AND RESULTS: 82 consecutive patients after repair of tetralogy of Fallot (TOF) who underwent cardiovascular magnetic resonance and echocardiography were studied. There was no difference in PRF between patients with moderate and severe right ventricular (RV) dilatation (32±13% vs. 37±12%; p=0.18). Significant difference in PRV was observed between these groups (23±10 ml/m2 vs. 31±12 ml/m2, respectively; p=0.02). PRV had better ability than PRF in identification of severe RV dilatation, both in group with RVOTO [area under the curve (AUC) 0.82 vs. 0.72, p=0.005] and in patients without RVOTO (AUC 0.83 vs. 0.77, p=0.04). A strong correlation was seen between PRF and PRV both in patients with and without RVOTO [r=0.93, p<0.0001 and r=0.92, p<0.0001, respectively]. In both subgroups high variability of PRF was found in subjects with similar degree of PRV. CONCLUSIONS: PRV shows better ability than PRF in evaluating influence of PR on RV in patients after TOF repair, both in population with and without concomitant RVOTO.

Cardiac magnetic resonance imaging in patients with Fabry's disease.

Fabry's disease (FD) is a rare hereditary disorder caused by the loss of alpha galactosidase A activity leading to accumulation of glycosphingolipids in various organs including hypertrophy of the heart. Most reports on cardiac involvement in FD focus on the left ventricular hypertrophy (LVH) and its relation to diastolic function. However, recent studies demonstrated large subset of patients with FD and right ventricle (RV) hypertophy. The accurate depiction of RV volumes, function and mass is possible with cardiovascular magnetic resonance (CMR). The CMR study can be also used to identify typically localised regions of intramyocardial fibrosis (infero-lateral segments of the LV), which have been shown to be a marker of inefficacious response to enzyme replacement therapy. We present series of 8 patients with genetically confirmed FD who underwent CMR study. We demonstrated a typical concentric and diffuse pattern of LVH with RV involvement in patients with the most severe LVH without significant impact on RV function and volumes. We showed that myocardial fibrosis can be observed not only in LV but also in RV. In 2 patients FD coexisted with symptomatic coronary artery disease with evidence of subendocardial myocardial fibrosis typical for ischaemic origin in one patient. The CMR confirmation of the presence of FD in one patient at an early stage of the disease, before the onset of advanced hypertrophy or failure of other organs, supports the value of this imaging technique in differential diagnosis of concentric and diffuse LVH.

Comparison between maximal left ventricular wall thickness and left ventricular mass in patients with hypertrophic cardiomyopathy.

BACKGROUND: Cardiovascular magnetic resonance enables accurate and reproducible assessment of left ventricular (LV) dimensions and function, free of geometric assumptions and limitations related to an inadequate acoustic window. In patients with hypertrophic cardiomyopathy (HCM), LV mass (LVM) and maximal LV wall thickness (MLVWT) have prognostic significance. AIM: To compare MLVWT and LVM in patients with HCM. METHODS: The study population included 33 patients with HCM (17 males, mean age 48.5 +/- 16.5 years). Subjects after alcohol septal ablation or surgical myectomy were excluded from the study. The MLVWT and LVM were measured with the use of cardiac magnetic resonance. The MLVWT was determined with the use of the dedicated software in short axis slices after manual definition of endocardial and epicardial contours. The LVM was indexed for body surface area and expressed in g/m(2). Cut-off values for normal, mildly increased and markedly increased LVM were based on previously published studies. RESULTS: Mean LVM in the whole study group was 107.4 +/- 30.9 g/m(2) (range 57.0-163.4 g/m(2)) and was higher in males than females (120.2 +/- 30.8 g/m(2) vs 93.8 +/- 25.3 g/m(2), respectively; p = 0.01). Mean MLVWT was 23.4 +/- 4.8 mm (range 16-36 mm). There was only a weak trend toward higher MLVWT in men when compared to women (24.8 +/- 5.4 mm vs 21.9 +/- 3.7 mm, respectively; p = 0.09). There was no correlation between LVM and MLVWT (r = 0.24; p = 0.17). A significant variability in LVM was observed in subjects with similar MLVWT; a greater than two-fold difference was noted in extreme cases. In three patients (9%; one female, two male) LVM was within the normal range and in another one female (3%) patient LVM was mildly increased. In the remaining patients (n = 29; 88%) markedly increased LVM was observed. CONCLUSIONS: The MLVWT does not reflect the degree of LV hypertrophy in patients with HCM. Patients with similar MLVWT may have substantial differences in LVM. A substantial group of patients with HCM is characterised by normal, or only mildly increased LVM, despite significant LV wall hypertrophy measured as MLVWT.

Late gadolinium enhancement gray zone in patients with hypertrophic cardiomyopathy. Comparison of different gray zone definitions.

To quantify heterogeneous tissue at the periphery of areas of fibrosis (gray zone) in patients with hypertrophic cardiomyopathy (HCM) with the use of two different techniques. Cardiac magnetic resonance with late gadolinium enhancement analysis was performed in 33 patients with HCM. Gray zone was evaluated with the use of two different techniques previously described in patients after myocardial infarction. LGE was present in 25 (78%) patients. There was no significant difference in total LGE mass at two different cut-off values [53.8 g (interquartile range, IQR 43.5-77.8 g) vs. 53.8 g (IQR 37.8-64.5 g), respectively, P = 0.49]. Significant difference in gray zone mass assessed with the use of two techniques was demonstrated (19.1 +/- 7.3 g vs. 50.8 +/- 47.8 g; P = 0.003). There was a strong correlation between total LGE and gray zone mass (r = 0.789, P = 0.0001 for first method and r = 0.951, P < 0.0001 for the second one, respectively). However, significant variability of gray zone mass (and extent expressed as % of left ventricular mass) in patients with similar LGE size/extent was observed. Moreover, LGE mass varied greatly in patients with similar gray zone size. Neither left ventricular mass, nor with maximal wall thickness correlated with extent of gray zone assessed with both methods. The studied techniques provided similar results with regard to total LGE but significant differences were observed in gray zone mass. Two patients may have similar extent (or absolute mass) of LGE, but strikingly discrepant gray zone size.

Comparison of different quantification methods of late gadolinium enhancement in patients with hypertrophic cardiomyopathy.

AIM: There is no consensus regarding the technique of quantification of late gadolinium enhancement (LGE). The aim of the study was to compare different methods of LGE quantification in patients with hypertrophic cardiomyopathy (HCM). METHODS: Cardiac magnetic resonance was performed in 33 patients with HCM. First, LGE was quantified by visual assessment by the team of experienced readers and compared with different thresholding techniques: from 1SD to 6SD above mean signal intensity (SI) of remote myocardium, above 50% of maximal SI of the enhanced area (full-width at half maximum, FWHM) and above peak SI of remote myocardium. RESULTS: LGE was present in 25 (78%) of patients. The median mass of LGE varied greatly depending on the quantification method used and was highest with the utilization of 1SD threshold [75.5 g, interquartile range (IQR): 63.3-112.3g] and lowest for FWHM method (8.4 g, IQR: 4.3-13.3g). There was no difference in mass of LGE as assessed with 6SD threshold and FWHM when compared to visual assessment (p=0.19 and p=0.1, respectively); all other thresholding techniques provided significant differences in the median LGE size when compared to visual analysis. Results for all thresholds, except FWHM were significantly correlated with visual assessment with the strongest correlation for 6SD (rho=0.956, p<0.0001). CONCLUSIONS: LGE quantification with the use of a threshold of 6SD above the mean SI of the remote myocardium provided the best agreement with visual assessment in patients with HCM.