Right atrial volume is a major determinant of tricuspid annulus area in functional tricuspid regurgitation: a three-dimensional echocardiographic study.

AIMS: The aim of this study is to explore the relationships of tricuspid annulus area (TAA) with right atrial maximal volume (RAVmax) and right ventricular end-diastolic volume (RVEDV) in healthy subjects and patients with functional tricuspid regurgitation (FTR) of different aetiologies and severities. METHODS AND RESULTS: We enrolled 280 patients (median age 66 years, 59% women) with FTR due to left heart disease (LHD), pulmonary hypertension (PH), corrected tetralogy of Fallot (TOF), chronic atrial fibrillation (AF), and 210 healthy volunteers (45 years, 53% women). We measured TAA at mid-systole and end-diastole, tenting volume of tricuspid leaflets, RAVmax, and RVEDV by 3D echocardiography. Irrespective of TA measurement timing, TAA correlated more closely with RAVmax than with RVEDV in both controls and FTR patients. On multivariable analysis, RAVmax was the most important determinant of TAA, accounting for 41% (normals) and 56% (FTR) of TAA variance. In FTR patients, age, RVEDV, and left ventricular ejection fraction were also independently correlated with TAA. RAVmax (AUC = 0.81) and TAA (AUC = 0.78) had a greater ability than RVEDV (AUC = 0.72) to predict severe FTR (P < 0.05). Among FTR patients, those with AF had the largest RAVmax and smallest RVEDV. RAVmax and TA were significantly dilated in all FTR groups, except in TOF. PH and TOF had largest RVEDV, yet tenting volume was increased only in PH and LHD. CONCLUSION: RA volume is a major determinant of TAA, and RA enlargement is an important mechanism of TA dilation in FTR irrespective of cardiac rhythm and RV loading conditions.

Prognostic validation of partition values for quantitative parameters to grade functional tricuspid regurgitation severity by conventional echocardiography.

AIMS: Quantitative echocardiography parameters are seldom used to grade tricuspid regurgitation (TR) severity due to relative paucity of validation studies and lack of prognostic data. To assess the relationship between TR severity and the composite endpoint of death and hospitalization for congestive heart failure (CHF); and to identify the threshold values of vena contracta width (VCavg), effective regurgitant orifice area (EROA), regurgitant volume (RegVol), and regurgitant fraction (RegFr) to define low, intermediate, and high-risk TR based on patients' outcome data. METHODS AND RESULTS: A cohort of 296 patients with at least mild TR underwent 2D, 3D, and Doppler echocardiography. We built statistical models (adjusted for age, NYHA class, left ventricular ejection fraction, and pulmonary artery systolic pressure) for VCavg, EROA, RegVol, and RegFr to study their relationships with the hazard of outcome. The tertiles of the derived hazard values defined the threshold values of the quantitative parameters for TR severity grading. During 47-month follow-up, 32 deaths and 72 CHF occurred. Event-free rate was 14%, 48%, and 93% in patients with severe, moderate, and mild TR, respectively. Severe TR was graded as VCavg > 6 mm, EROA > 0.30 cm2, RegVol > 30 mL, and RegF > 45%. CONCLUSION: This outcome study demonstrates the prognostic value of quantitative parameters of TR severity and provides prognostically meaningful threshold values to grade TR severity in low, intermediate, and high risk.

Functional Regurgitation of Atrioventricular Valves and Atrial Fibrillation: An Elusive Pathophysiological Link Deserving Further Attention.

In patients with structurally normal atrioventricular valvular apparatus, functional regurgitation of the mitral or tricuspid valves has been attributed mainly to ventricular dilation and/or dysfunction, through a combination of annulus dilation and tethering of the valve leaflets. The occurrence of functional regurgitation of atrioventricular valves in patients with long-standing persistent atrial fibrillation and atrial dilation but normal ventricular size and function has received much less attention, and its peculiar mechanisms still remain to be understood. This distinct form of functional regurgitation (i.e., "atrial functional regurgitation") may require different treatment and interventional repair approaches than the classical functional regurgitation due to ventricular dilatation and dysfunction ("ventricular functional regurgitation"), and current guideline recommendations do not yet address this distinction. Clarifying the differences in the pathophysiology of atrial functional regurgitation and its management implications is of paramount importance. This review describes briefly the comparative anatomy of mitral and tricuspid apparatus and the pathophysiology and typical echocardiographic features of atrial functional regurgitation compared with ventricular functional regurgitation, as well as the added value of three-dimensional echocardiography as an essential imaging tool to clarify the mechanisms involved in its development.

[Current clinical applications of three-dimensional echocardiography]. / Principali applicazioni dell'ecocardiografia tridimensionale nell'attuale pratica clinica.

Three-dimensional echocardiography (3DE) represents one of the most innovative advances in cardiovascular imaging over the last 20 years. Recent technological developments have fueled the full implementation of 3DE in clinical practice and expanded its impact on patient diagnosis, management, and prognosis. One of the most important clinical applications of transthoracic 3DE has been the quantitation of cardiac chamber volumes and function. The main limitations affecting two-dimensional echocardiography calculations of chamber volumes (i.e. geometric assumptions about cardiac chamber shape and view foreshortening) are overcome by 3DE that allows an actual measurement of their volumes. Transesophageal 3DE has been applied mainly to assess the anatomy and function of heart valves, congenital defects and masses in the beating heart. As reparative cardiac surgery and transcatheter procedures have become more and more popular to treat structural heart disease, transesophageal 3DE has become not only one of the main imaging modalities for procedure planning but also for intra-procedural guidance and assessment of procedural results. New image rendering modalities such as 3D printing, holographic display, and fusion of 3DE images with other radiological or nuclear modalities will further expand the clinical applications and indications of 3DE.

Three-dimensional echocardiography to assess left ventricular geometry and function.

Introduction: Quantification of left ventricular (LV) size and function represents the most frequent indication for an echocardiographic study. New echocardiographic techniques have been developed over the last decades in an attempt to provide a more comprehensive, accurate, and reproducible assessment of LV function.Areas covered: Although two-dimensional echocardiography (2DE) is the recommended imaging modality to evaluate the LV, three-dimensional echocardiography (3DE) has proven to be more accurate, by avoiding geometric assumptions about LV geometry, and to have incremental value for outcome prediction in comparison to conventional 2DE. LV shape (sphericity) and mass are actually measured with 3DE. Myocardial deformation analysis using 3DE can early detect subclinical LV dysfunction, before any detectable change in LV ejection fraction.Expert opinion: 3DE eliminates the errors associated with foreshortening and geometric assumptions inherent to 2DE and 3DE measurements approach very closely those obtained by CMR (the current reference modality), while maintaining the unique clinical advantage of a safe, highly cost/effective, portable imaging technique, available to the cardiologist at bedside to translate immediately the echocardiography findings into the clinical decision-making process.

Morphological Assessment of the Tricuspid Apparatus and Grading Regurgitation Severity in Patients With Functional Tricuspid Regurgitation: Thinking Outside the Box.

Current guidelines recommend transthoracic echocardiography to assess patients with functional tricuspid regurgitation (FTR) because it provides information regarding the presence of structural abnormalities of the tricuspid valve (TV), allows measurement of tricuspid annulus diameter, and evaluates severity of FTR by integrating data obtained from 2D and Doppler echocardiography. Critical components of the noninvasive evaluation include information regarding TV anatomy, tricuspid regurgitation severity, right ventricular size and systolic function, and associated findings such as estimated pulmonary artery pressure. However, most of the parameters included in the current recommendations to assess FTR are derived from the experience and knowledge developed about the mitral valve and have been transferred from the left to the right side of the heart without accounting for differences in anatomy of the tricuspid and mitral apparatus or for differences in hemodynamic environment in which the TV operates compared to its left counterpart.

Assessment of Multi-Ion Channel Block in a Phase I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study.

Balanced multi-ion channel-blocking drugs have low torsade risk because they block inward currents. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative proposes to use an in silico cardiomyocyte model to determine the presence of balanced block, and absence of heart rate corrected J-Tpeak (J-Tpeak c) prolongation would be expected for balanced blockers. This study included three balanced blockers in a 10-subject-per-drug parallel design; lopinavir/ritonavir and verapamil met the primary end point of ΔΔJ-Tpeak c upper bound < 10 ms, whereas ranolazine did not (upper bounds of 8.8, 6.1, and 12.0 ms, respectively). Chloroquine, a predominant blocker of the potassium channel encoded by the ether-à-go-go related gene (hERG), prolonged ΔΔQTc and ΔΔJ-Tpeak c by ≥ 10 ms. In a separate crossover design, diltiazem (calcium block) did not shorten dofetilide-induced ΔQTc prolongation, but shortened ΔJ-Tpeak c and prolonged ΔTpeak -Tend . Absence of J-Tpeak c prolongation seems consistent with balanced block; however, small sample size (10 subjects) may be insufficient to characterize concentration-response in some cases.

Sex Differences of Patients With Systemic Hypertension (From the Analysis of the Systolic Blood Pressure Intervention Trial [SPRINT]).

There are differences in the incidence, pathophysiology, and long-term effects of hypertension between women and men. We assessed sex-specific benefit-risk tradeoffs of different blood pressure (BP) goals in patients enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT) after propensity score matching those with standard therapy (systolic BP <140 mm Hg) to those with intensive therapy (systolic BP <120 mm Hg; n = 9,106). Cox regression was conducted to compare standard versus intensive therapy in women and men with the composite outcome of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Women were generally healthier at baseline and had a lower cardiovascular risk. Men on intensive therapy had a lower risk of the composite outcome compared to those on standard therapy (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.57 to 0.86, p = 0.001) while in women no differences between therapy groups were observed (HR 0.82 [0.60 to 1.12], p = 0.206). For safety outcomes, women and men had increased risk of related serious adverse events with intensive treatment (HR 1.52 [1.06 to 2.18], p = 0.023 and HR 2.07 [1.55 to2.77], p < 0.001, respectively). In conclusion, our study demonstrated that women did not benefit from intensive compared to standard BP control. A potential explanation for this may be the lower baseline cardiovascular risk in women.

The 43rd International Society for Computerized Electrocardiology ECG initiative for the automated detection of strict left bundle branch block.

The presence of left bundle branch block (LBBB) is an important predictor of benefit from cardiac resynchronization therapy (CRT). New "strict" electrocardiographic (ECG) criteria for LBBB have been shown to better predict benefit from CRT. The "strict" LBBB criteria include: QRS duration ≥140 ms (men) or ≥130 ms (women), QS- or rS-configurations of the QRS complex in leads V1 and V2, and mid-QRS notching or slurring in ≥2 of leads V1, V2, V5, V6, I and aVL. The "strict" LBBB criteria are not regularly used and most hospital automated ECG systems and physicians still use more conventional LBBB criteria. As part of the 43rd International Society for Computerized Electrocardiology (ISCE) meeting, we conducted an initiative on the automated detection of "strict" LBBB where industry and academic investigators could present their algorithm results on digital 12-lead ECGs with varying QRS morphologies from the MADIT-CRT trial (300 training and 302 test set ECGs that were manually adjudicated for "strict" LBBB presence). The results revealed a 64-82% accuracy, 48-76% sensitivity and 46-87% specificity for automated "strict" LBBB detection from 7 participants. Most mismatches were likely attributed to differences in detection and absence of specific definitions for notches and slurs while differences in QRS duration and S-waves in leads V1 and V2 were less problematic. The full unblinded training and test datasets including all ECG signals are being made available through the Telemetric and Holter ECG Warehouse (THEW) for further exploration.