Sudden cardiac death: the pro-arrhythmic interaction of an acute loading with an underlying substrate.

Sudden cardiac death (SCD) is a complex phenomenon, occurring either in apparently normal individuals or in those where there is a recognized underlying cardiac abnormality. In both groups, the lethal arrhythmia has frequently been related to the physiologic trigger of either exercise or stress. Prior research into SCD has focused mainly on a combination of identifying either vulnerable myocardial substrates; pharmacological approaches to altering electrical activation/repolarisation in substrates; or the suppression of induced lethal arrhythmias with implantable defibrillators. However, it has been suggested that in a significant number of cases, the interaction of a transient induced trigger with a pre-existing electrical or mechanical substrate is the basis for the induction of the sustained lethal arrhythmia. In this manuscript we will discuss the precise mechanisms whereby one of such potential physiologic trigger: an acute change in systolic blood pressure, can induce a sequence of alterations in global and local cardiac mechanics which in turn result in regional left ventricular post-systolic deformation which, mediated (through stretch-induced changes in local mechano-electrical coupling) provokes local electrical after-depolarisations which can spill over into complex runs of premature ventricular beats. These local acute pressure/stretch induced runs of ventricular ectopy originate in either basal or apical normal myocardium and, in combination with a co-existing distal pro-arrhymic substrate, can interact to induce a lethal arrhythmia.

In memoriam Liv Hatle 1936-2023, pioneering echocardiologist.

Professor Liv Hatle died in June 2023. In Trondheim, Norway, in the mid-1970s she was the first cardiologist to be given access to a PEDOF Doppler ultrasound system for clinical examinations, which she used to investigate cardiovascular haemodynamics non-invasively. She went on to establish methods for estimating valve gradients, pulmonary arterial pressure, and left ventricular diastolic function, that are still used today in millions of patients worldwide.

Successful ablation for atrioventricular nodal reentrant tachycardia in a patient with left atrial isomerism.

Left atrial isomerism (LAI) is characterized by the presence of two morphologically identical atria. It is commonly associated with conduction defects. We report a case of LAI presenting with highly symptomatic atrioventricular nodal reentrant tachycardia, which was cured by ablation.

A concise history of echocardiography: timeline, pioneers, and landmark publications.

Echocardiography is less than 70 years old, and many major advances have occurred within living memory, but already some pioneering contributions may be overlooked. In order to consider what circumstances have been common to the most successful innovations, we have studied and here provide a timeline and summary of the most important developments in transthoracic and transoesophageal ultrasound imaging and Doppler techniques, as well as in intravascular ultrasound and imaging in paediatric cardiology. The entries are linked to a comprehensive list of first publications and to a collection of first-hand historical accounts published by early investigators. Review of the original manuscripts highlights that it is difficult to establish unequivocal precedence for many new imaging methods, since engineers were often working independently but simultaneously on similar problems. Many individuals who are prominently linked with particular developments were not the first in their field. Developments in echocardiography have been highly dependent on technological advances, and most likely to be successful when engineers and clinicians were able to collaborate with open exchange between centres and disciplines. As with many other new medical technologies, initial responses were sceptical and introduction into clinical practice required persistence and substantial energy from the first adopters. Current developments involve advances in software as much as in equipment, and progress will depend on continuing collaborations between engineers and clinical scientists, for example to identify unmet needs and to investigate the clinical impact of particular imaging approaches.

Assessment of aortic stiffness in marfan syndrome using two-dimensional and Doppler echocardiography.

BACKGROUND: Extracellular matrix remodeling in the aortic wall results in increased aortic stiffness (AoS) in Marfan syndrome (MFS). Pulsed-wave velocity (PWV) constitutes the best indirect AoS measurement. We aimed to assess PWV in MFS patients using two-dimensional (2D) and Doppler echocardiography. METHODS: Thirty-one MFS patients, (mean age 31 ± 14 years, 16 men) and 31 controls were examined. Blood flow was recorded in the aorta near the aortic valve and immediately after in the descending aorta with simultaneous electrocardiography. PWV was calculated by dividing the distance between the two sample volume positions (D) by the time difference (TD) between the intervals from the QRS start to the ascending and descending aortic flow onsets. B-stiffness was also measured. RESULTS: TD (described in "Methods" section) and, aortic arch length were significantly increased in MFS patients, P < 0.001. Thus, PWV values were significantly higher in patients when compared with controls, 7.20 m/s (5.12, 9.43) versus 4.64 m/s (3.37, 6.24), P < 0.001. B-stiffness was also significantly increased in MFS patients; 5.15 (3.69, 7.65) versus 2.44 (1.82, 3.66), P < 0.001. Multiple regression analysis showed a positive association with MFS diagnosis and age, (P = 0.002 and 0.009, respectively). Reproducibility of PWV measurements was <5%. CONCLUSIONS: AoS was significantly higher in MFS patients as expected. Our data demonstrated that PWV measurements can be performed, in the absence of serious musculoskeletal abnormalities in MFS adults, as part of a cardiac ultrasound scan. This technique can be helpful in diagnosis and management in MFS.

Impaired biventricular deformation in Marfan syndrome: a strain and strain rate study in adult unoperated patients.

OBJECTIVE: To investigate the presence of any regional myocardial deformation abnormalities in Marfan syndrome (MFS) and determine the benefits of using advanced echocardiography compared to conventional techniques. BACKGROUND: Myocardial dysfunction in MFS may be caused by extracellular matrix remodeling thus, resulting in uniform reduced functionality. However, increased aortic stiffness may cause segmental ventricular abnormalities. Strain rate imaging (SRI) constitutes a validated technique to assess regional deformation in various clinical conditions. With this in mind, we aimed to investigate biventricular function in MFS using SRI. METHODS: Forty-four MFS patients (mean age 30 ± 12 years, 26 men) and 49 controls without valvular disease were examined using SRI. Ejection fraction (EF) was calculated by the Simpson's biplane method. Biventricular deformation was assessed by measuring strain/strain rate. Strain values were divided by left ventricular (LV) end-diastolic volume to adjust LV deformation for geometry changes providing a strain index (SI). Aortic stiffness was evaluated using the ß-stiffness index. RESULTS: EF (%) was reduced in MFS patients (59 ± 5 vs 72 ± 4, P < 0.001), whereas ß-stiffness was increased (P < 0.001). LV radial and LV and right ventricular (RV) long-axis strain values (%) were reduced in the patient group (70 ± 17 vs 93 ± 10; 19 ± 2 vs 25 ± 2; 30 ± 9 vs 36 ± 8, respectively, P < 0.001). Strain rate measurements were also reduced (P < 0.001). In a multiple regression analysis, MFS diagnosis was negatively associated with LV SI (-0.262 [-0.306, -0.219], P < 0.001). ß-Stiffness was negatively associated with SI obtained from the septum, inferior and anterior walls. ROC analyses demonstrated that SRI, when compared with conventional echocardiography, had higher sensitivity and specificity in predicting biventricular dysfunction in MFS. CONCLUSIONS: Our study showed a uniform reduction in biventricular deformation in MFS. These findings suggest that assessment of myocardial function using advanced echocardiographic techniques could be more accurate in MFS patient evaluation than conventional echocardiography alone.

Low-dose dobutamine stress echo to quantify the degree of remodelling after cardiac resynchronization therapy.

AIMS: Presence of contractile reserve during low-dose dobutamine stress echo (DSE) appears predictive of cardiac resynchronization therapy (CRT) outcome. We hypothesize that changes in left bundle branch block (LBBB)-induced dyssynchronous motion during low-dose DSE could be related to the extent of reverse remodelling. METHODS AND RESULTS: Fifty-two patients (69 +/- 2 years, EF: 24 +/- 7%, QRS > 120 ms) were studied pre- and post-CRT (7 +/- 1 months). Reduction in left ventricular end-systolic volume (LVESV) >/=10% defined response. A clinical improvement was sought additionally prior to implant and after CRT (NYHA class reduction >1), increase in 6 min walk test (>10%), and fall in BNP (>/=30%). To identify the presence of septal scar and its impact on our assessment during low-dose DSE, a cardiac magnetic resonance was performed pre-CRT. Presence of an abnormal short-lived septal motion occurring during the isovolumic contraction time [septal flash (SF)] identified LBBB-induced dyssynchrony. Septal flash extent was quantified from M-mode and radial velocity traces. At baseline, 31/52 patients had an SF. In all patients, DSE increased SF. Twenty-nine out of thirty-one patients responded with reverse remodelling post-CRT. The degree of peak low-dose stress SF correlated with the extent of reverse remodelling (R = 0.6, P < 0.0001). Additionally, SF increase correlated with greater fall in BNP post-CRT (R = 0.4, P = 0.01). Among patients with no SF at rest (21/52 patients), low-dose DSE induced an SF and a fall in stroke volume (SV) in five patients who all showed reverse remodelling after CRT. With low-dose DSE, the remaining 16 patients all failed to demonstrate a SF, and all but one patient with additional atrioventricular dyssynchrony were non-responders. CONCLUSION: Low-dose DSE increases and unmasks LBBB-induced dyssynchronous motion, easing its detection. The degree of clinical and echocardiographic response correlated with the extent of peak SF seen during low-dose DSE.

Velocity and deformation imaging for the assessment of myocardial dysfunction.

Recent developments in echocardiographic imaging technology and processing enabled the quantification of myocardial motion and deformation in a clinical setting. Echocardiographic strain (-rate) imaging provides a relatively easy way to study myocardial deformation. However, although (local) deformation is clearly linked to cardiac (dys-) function, it is important to understand how this information can be used in clinical practice and how specific deformation patterns should be interpreted. This review paper first discusses which issues are important to address when assessing cardiac function and how (regional) deformation and myocardial contractility are related. The use and interpretation of deformation profiles is further illustrated for some typical cardiac pathologies. The observed deformation patterns are discussed in light of the changes in regional contractility (ischemia), timing of contractile force development (LBBB and heart failure), pressure/volume overload, and assessing diastolic function.

Myocardial deformation abnormalities in patients with aortic regurgitation: a strain rate imaging study.

AIMS: Early left ventricular (LV) dysfunction in asymptomatic patients with severe aortic regurgitation (AR) may go undetected due to the lack of a sufficiently sensitive diagnostic tool. Ultrasonic strain/strain rate (S/SR) imaging should now provide such sensitivity in detecting early dysfunction in regional LV systolic deformation. The aim of this study was to understand and define the changes in LV regional systolic deformation based on S/SR imaging in patients with asymptomatic or minimally symptomatic AR. METHODS AND RESULTS: Eighty-one individuals were studied: 59 asymptomatic patients with isolated non-ischaemic AR who were divided into three sub-groups such as mild, moderate, and severe AR and 22 age-matched healthy subjects. All patients underwent standard echocardiographic examinations including a tissue Doppler imaging study. For LV radial deformation, the posterior wall (LVPW) was examined. To assess LV longitudinal deformation, S and SR data were acquired from the LV lateral wall and septum. Radial as well as longitudinal peak systolic SRs were significantly decreased in patients with both moderate AR (LVPW, P=0.0009; septum, P=0.03; LV lateral wall, P=0.0009) and severe AR (P<0.0001) compared with healthy subjects. Changes in regional LV deformation correlated inversely both with LV end-diastolic volume and with end-systolic volume. CONCLUSIONS: Strain rate imaging is a sensitive tool in detecting the spectrum of changes in radial and longitudinal deformation in asymptomatic or minimally symptomatic patients with AR. The index where volume was corrected by deformation should form the basis for predicting subclinical LV dysfunction in patients with increasing LV dilatation.

Left ventricular size determines tissue Doppler-derived longitudinal strain and strain rate.

AIMS: Tissue Doppler-derived indices of strain (epsilon) and strain rate (SR) have been developed to assess regional cardiac function. However, the effect of left ventricular (LV) size on epsilon and SR has not been studied in depth. The aim of this study was to assess to what extent heart size influence epsilon or SR. METHODS AND RESULTS: In 21 anaesthetized pigs ranging from 12.5 to 70.0 kg, tissue Doppler-derived epsilon and SR, and haemodynamic parameters, were assessed during controlled heart rates and different loading conditions. dP/dt did not correlate to pig weight, suggesting constant contractility during growth. Longitudinal epsilon and SR were significantly higher in smaller compared with larger hearts. The hyperbolic correlation between pigs weight and epsilon and SR was r(2)=0.621 and 0.372, respectively, both P<0.0001. Afterload elevation induced a reduction in longitudinal epsilon (from -24.2+/-3.2 to -12.1+/-5.5%, P=0.001) and SR (from -2.3+/-0.8 to -1.3+/-2.4 s(-1), P=0.034), whereas increasing preload increased epsilon (from -26.4+/-10.3 to -38.1+/-14.3%, P=0.006) and SR (from -2.3+/-0.9 to -4.22+/-1.8 s(-1), P=0.002). CONCLUSION: Longitudinal epsilon and SR decrease with increasing LV dimensions in spite of an unaltered contractility. These results show and confirm that heart size influences epsilon and SR, which are highly load-dependent parameters.

Impaired right ventricular systolic function demonstrated by reduced atrioventricular plane displacement in adults with Marfan syndrome.

AIMS: The right ventricle (RV) ejects the same volume of blood at the same rate as the left ventricle (LV). Mild LV dysfunction has been demonstrated in Marfan syndrome (MFS). However, little attention has been paid to the functioning of the RV. The aim of this study was to assess RV function in unoperated adult MFS patients. METHODS AND RESULTS: In 66 unoperated (15-58 years) MFS patients and 61 controls, rate of pressure rise (dp/dt) in RV, and tricuspid annular motion (TAM) were studied using conventional echocardiography and tissue Doppler imaging (TDI). When compared with controls, MFS patients showed impaired RV systolic function as expressed by a reduced dp/dt, TAM obtained by M-mode echocardiography, and peak TDI systolic velocities at the basal lateral wall (745.36+/-37.85 vs. 1103.30+/-27.30 mmHg, P<0.001; 2.2+/-0.05 vs. 2.5+/-0.05 cm, P<0.001; and 0.13+/-0.002 vs. 0.16+/-0.002 m/s, P<0.001, respectively). CONCLUSION: This study demonstrated a primary impairment of RV systolic function in MFS. This is the first study to report RV dysfunction in MFS. Such data could prove valuable during the peri-operative and long-term medical management of MFS patients.

Biventricular and atrial diastolic function assessment using conventional echocardiography and tissue-Doppler imaging in adults with Marfan syndrome.

AIMS: Previous studies provided evidence about left ventricular systolic and diastolic dysfunction in adults with Marfan syndrome (MFS). However, in the literature, data on right ventricular and bi-atrial diastolic function are limited. We aimed to investigate whether, in the absence of significant valvular disease, diastolic dysfunction is present not only in both ventricles but also in the atrial cavities. METHODS AND RESULTS: Seventy-two adult unoperated MFS patients and 73 controls without significant differences in age, sex, and body surface area from the patient group were studied using two-dimensional, pulsed, and colour-Doppler and tissue-Doppler imaging (TDI). Biventricular early filling measurements were significantly decreased in MFS patients when compared with controls (P < 0.001). Pulsed TDI early filling measurements obtained from five mitral annular regions and over the lateral tricuspid valve corner were significantly reduced in the patient group (P < 0.001). Indices reflecting atrial function at the reservoir, conduit and contractile phases were also significantly decreased in MFS patients (P < 0.001). CONCLUSION: This study demonstrated significant biventricular diastolic and biatrial systolic and diastolic dysfunction in MFS patients. Our findings suggest that MFS affects diastolic function independently. Diastolic abnormalities could be attributed to fibrillin-1 deficiency and dysregulation of transforming growth factor-beta activity in the cardiac extracellular matrix.

Assessment of carotid compliance using real time vascular ultrasound image analysis in Marfan syndrome.

BACKGROUND: Fibrillin-1 deficiency, dysregulated cytokine transforming growth factor-beta, and increased collagen deposition related to fibrillin-1 gene mutations could predispose to impaired carotid compliance (CC) in Marfan syndrome (MFS). We sought to detect any alterations in CC using the vascular image analysis system (VIA). METHODS AND RESULTS: Thirty-two MFS patients, 20 men and 12 women (mean age 34.2 +/- 12.05 years), and 29 controls matched for age, sex, and body surface area (BSA) were recruited. The entire length of each carotid system was initially scanned longitudinally using a 14 MHz linear transducer. Then, a stereotactic clamp held the transducer in contact with the carotid artery. Arterial diameter changes during the cardiac cycle were recorded for 1 minute from both right (RCCA) and left common carotid arteries (LCCA) separately using the VIA system. RCCA and LCCA compliance and distensibility measurements were significantly reduced in MFS patients when compared to controls, P < 0.05. RCCA and LCCA intima-media thickness did not differ between patients and controls, P > 0.05. MFS diagnosis and age were associated with reduced CC in both carotid arteries after adjusting for variables such as, sex, BSA, heart rate, beta-blockade, intima-media thickness, and aortic root size. CONCLUSIONS: Our findings showed a reduction in CC in adult patients with MFS. This could be attributed to fibrillin-1 deficiency resulting in structural abnormalities in the carotid arterial wall.

Usefulness of changes in left ventricular wall thickness to predict full or partial pressure reperfusion in ST-elevation acute myocardial infarction.

Experimental studies have shown that if an acute transmural myocardial infarction is reperfused at full pressure there is an immediate and persisting increase in end-diastolic wall thickness (EDWT) due to massive intramural edema, with the amount of edema inversely related to the residual stenosis in the infarct-related artery. This study investigated if these findings are paralleled in the clinical setting and whether the resultant myocardial substrate differs after percutaneous coronary intervention (PCI) versus thrombolysis (the latter having a higher incidence of residual flow limiting stenosis in the culprit vessel). Eighty-eight consecutive patients with ST-elevation myocardial infarction were enrolled. Twenty-seven patients underwent primary PCI, 23 had rescue PCI, and 38 had thrombolysis. Standard M-mode and 2-dimensional echocardiographies were performed within 12 hours. Regional EDWT was measured in 904 infarct-related segments after the different reperfusion strategies and compared with 504 remote noninfarcted segments. EDWT of infarct-related segments after primary PCI was significantly increased compared with normal segments. At follow-up, after 6 months, EDWT of these segments was significantly decreased, indicating transmural infarction. EDWT of infarct-related segments after thrombolysis did not differ from that of normal segments. After rescue PCI, EDWT of infarct-related segments was significantly decreased compared with that of normal segments. In conclusion, full-pressure restoration of epicardial blood flow after transmural myocardial infarction causes an immediate increase in EDWT, easily detected by echocardiography. In contrast, pressure-limiting reperfusion (typical for thrombolysis) resultsin normal EDWT. This confirms experimental data that PCI and thrombolysis can differ in their resultant myocardial substrate.

Right ventricular outflow and apical pacing comparably worsen the echocardiographic normal left ventricle.

AIMS: A depressed left ventricular function (LVF) is sometimes observed during right ventricular apical (RVA) pacing, but any prediction of this adverse effect cannot be done. Right ventricular outflow tract (RVOT) pacing is thought to deteriorate LVF less frequently because of a more normal LV activation pattern. This study aims to assess the acute effects of RVA and RVOT pacing on LVF in order to determine the contribution of echocardiography for the selection of the optimum pacing site during pacemaker (PM) implantation. METHODS AND RESULTS: Fourteen patients with a DDD-pacemaker (7 RVA, 7 RVOT) and normal LVF without other cardiac abnormalities were studied. PM dependency, because of sick sinus syndrome with normal atrioventricular and intraventricular conduction, was absent in all, allowing acute programming changes. Wall motion score (WMS), longitudinal LV strain, and tissue Doppler imaging for electromechanical delay were assessed with echocardiography during AAI pacing constituting baseline and DDD pacing. The WMS was normal at baseline (AAI pacing) in all patients and LV dyssynchrony was absent. Acute RVA and RVOT pacing deteriorated WMS, electromechanical delay, and longitudinal LV strain, but no difference of the deterioration between both pacing sites was present and dyssynchrony did not emerge. CONCLUSION: Both acute RVA and RVOT pacing negatively affect WMS, longitudinal LV strain, and mechanical activation times, without clear differences between both pacing sites. Thus echocardiographic techniques do not facilitate the selection between RVOT and RVA pacing to exclude adverse effects on LVF during PM implantation in patients with a normal LVF.

Early impairment of left ventricular long-axis systolic function demonstrated by reduced atrioventricular plane displacement in patients with Marfan syndrome.

AIMS: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene. It has been observed that FBN1 deficient mice have reduced left ventricular (LV) systolic function which is correlated to increased transforming growth factor-beta activity. This study aimed to ascertain LV functional abnormalities in MFS patients using M-mode and tissue Doppler imaging (TDI). METHODS AND RESULTS: In 66 (15-58 years) MFS patients and 61 normal controls, ejection fraction (EF) was evaluated by Simpson's biplane method. Atrioventricular plane displacement (AVPD) obtained from five mitral annular regions was also assessed using M-mode and TDI techniques. To overcome limitations associated with conventional M-mode echocardiography, anatomical and colour anatomical M-mode were also utilized. Ejection fraction was significantly reduced in MFS patients when compared to controls (66.3 +/- 0.74 vs. 71.9 +/- 0.56, P < 0.001), although it was within the normal range. M-mode and TDI AVPD measurements obtained from lateral, septal, inferior, anterior and posterior mitral annular regions were also significantly reduced in MFS patients in comparison to controls (P <0.001, for all measurements). CONCLUSION: Left ventricular long-axis systolic function is significantly reduced in MFS patients. This data suggests that LV function should be monitored in MFS and appropriate treatment applied if necessary.

Regional left ventricular deformation and geometry analysis provides insights in myocardial remodelling in mild to moderate hypertension.

AIM: In the early stages of hypertension (HTN), when global left ventricular (LV) function is still unaffected, localized geometrical changes suggest changes in regional function. We investigated regional geometry and systolic deformation (using strain/strain rate (S/SR) imaging) in HTN. METHODS AND RESULTS: We studied 74 untreated mild to moderate HTNs and 34 matched normotensives (NTN). All had a standard echo including myocardial velocity data for regional radial and longitudinal deformation. Despite the absence of abnormalities in standard functional indices and LVH, non-uniform changes in regional geometry and deformation were observed. Besides a significant increase in wall thickness (WT) in all HTN segments, there was a gradual increase in WT from apex to base resulting in prominent basal septal hypertrophy. In HTN, regional longitudinal peak systolic SR (SSR) and end-systolic S (ESS) were significantly (P < 0.0001) reduced in the basal septum. In the lateral wall there was an increase in peak SSR and ESS (P < 0.05) basally. The basal septal ESS correlated both with mean arterial pressure and basal septal WT, with lower ESS for higher BP and thicker septum. CONCLUSION: Regionally differing geometrical remodelling occurs early in HTN. Longitudinal ESS and peak SSR are sensitive markers of early changes occurring in HTN.

Full or pressure limited reperfusion of an acute myocardial infarct results in a different wall thickness and deformation of the distal myocardium--implications for clinical reperfusion strategies.

AIM: The study aim was to determine the sequence of changes in both wall thickness and function in 'at risk' myocardium (using M-mode and radial strain/strain-rate imaging) induced by reperfusion of an acute transmural infarction, and to relate these changes to the presence or absence of a pressure-limiting stenosis in the infarct related epicardial vessel. METHODS: Eighteen closed-chest pigs were randomized into two groups (each with nine animals). In Group I, 4 weeks prior to induction of an acute transmural infarct, a copper coated stent was implanted in the proximal circumflex artery (Cx) to create a coronary artery stenosis of between 30 and 95% lumen diameter. At 4 weeks, the stenotic Cx vessel was occluded for 90 min by inflation of a PTCA balloon placed proximal to the stenosis to produce an acute transmural infarction. In Group II (the control group), 90 min Cx occlusion was performed in a normal vessel. In both groups the resulting acute transmural infarction was reperfused after 90 min by removing the PTCA balloon. For both groups, cardiac ultrasound data, including strain/strain-rate imaging, were collected at all stages of the investigation for subsequent offline analysis. RESULTS: In both groups, acute reperfusion (TIMI flow 3 or 2), immediately increased infarct zone end-diastolic wall thickness due to the development of oedema. The acute increase in wall thickness was significantly higher in the non-stenotic animals as compared to the ones with a residual stenosis. Neither of the groups showed any tendency to normalize deformation (strain) during the reperfusion period. CONCLUSION: In this experimental study, the measurement of end-diastolic wall thickness was a simple and non-invasive tool to monitor acute infarct reperfusion. It also provided information on the presence of a flow limiting stenosis in the infarct related artery after restoration of the flow. The deformation of the myocardium remained impaired during early reperfusion, whether reflow was at full pressure or low pressure due to a residual stenosis in the infarct related artery.