Prediction of diagnosis and diastolic filling pressure by AI-enhanced cardiac MRI: a modelling study of hospital data.

BACKGROUND: With increasing numbers of patients and novel drugs for distinct causes of systolic and diastolic heart failure, automated assessment of cardiac function is important. We aimed to provide a non-invasive method to predict diagnosis of patients undergoing cardiac MRI (cMRI) and to obtain left ventricular end-diastolic pressure (LVEDP). METHODS: For this modelling study, patients who had undergone cardiac catheterisation at University Hospital Heidelberg (Heidelberg, Germany) between July 15, 2004 and March 16, 2023, were identified, as were individual left ventricular pressure measurements. We used existing patient data from routine cardiac diagnostics. From this initial group, we extracted patients who had been diagnosed with ischaemic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, or amyloidosis, as well as control individuals with no structural phenotype. Data were pseudonymised and only processed within the university hospital's AI infrastructure. We used the data to build different models to predict either demographic (ie, AI-age and AI-sex), diagnostic (ie, AI-coronary artery disease and AI-cardiomyopathy [AI-CMP]), or functional parameters (ie, AI-LVEDP). We randomly divided our datasets via computer into training, validation, and test datasets. AI-CMP was not compared with other models, but was validated in a prospective setting. Benchmarking was also done. FINDINGS: 66 936 patients who had undergone cardiac catheterisation at University Hospital Heidelberg were identified, with more than 183 772 individual left ventricular pressure measurements. We extracted 4390 patients from this initial group, of whom 1131 (25·8%) had been diagnosed with ischaemic cardiomyopathy, 1064 (24·2%) had been diagnosed with dilated cardiomyopathy, 816 (18·6%) had been diagnosed with hypertrophic cardiomyopathy, 202 (4·6%) had been diagnosed with amyloidosis, and 1177 (26·7%) were control individuals with no structural phenotype. The core cohort only included patients with cardiac catherisation and cMRI within 30 days, and emergency cases were excluded. AI-sex was able to predict patient sex with areas under the receiver operating characteristic curves (AUCs) of 0·78 (95% CI 0·77-0·78) and AI-age was able to predict patient age with a mean absolute error of 7·86 years (7·77-7·95), with a Pearson correlation of 0·57 (95% CI 0·56-0·57). The AUCs for the classification tasks ranged between 0·82 (95% CI 0·79-0·84) for ischaemic cardiomyopathy and 0·92 (0·91-0·94) for hypertrophic cardiomyopathy. INTERPRETATION: Our AI models could be easily integrated into clinical practice and provide added value to the information content of cMRI, allowing for disease classification and prediction of diastolic function. FUNDING: Informatics for Life initiative of the Klaus-Tschira Foundation, German Center for Cardiovascular Research, eCardiology section of the German Cardiac Society, and AI Health Innovation Cluster Heidelberg.

Right ventricular energy metabolism in a porcine model of acute right ventricular pressure overload after weaning from cardiopulmonary bypass.

Acute right ventricular pressure overload (RVPO) occurs following congenital heart surgery and often results in low cardiac output syndrome. We tested the hypothesis that the RV exhibits limited ability to modify substrate utilization in response to increasing energy requirements during acute RVPO after cardiopulmonary bypass (CPB). We assessed the RV fractional contributions (Fc) of substrates to the citric acid cycle in juvenile pigs exposed to acute RVPO by pulmonary artery banding (PAB) and CPB. Sixteen Yorkshire male pigs (median 38 days old, 12.2 kg of body weight) were randomized to SHAM (Ctrl, n = 5), 2-h CPB (CPB, n = 5) or CPB with PAB (PAB-CPB, n = 6). Carbon-13 (13 C)-labeled lactate, medium-chain, and mixed long-chain fatty acids (MCFA and LCFAs) were infused as metabolic tracers for energy substrates. After weaning from CPB, RV systolic pressure (RVSP) doubled baseline in PAB-CPB while piglets in CPB group maintained normal RVSP. Fc-LCFAs decreased significantly in order PAB-CPB > CPB > Ctrl groups by 13 C-NMR. Fc-lactate and Fc-MCFA were similar among the three groups. Intragroup analysis for PAB-CPB showed that the limited Fc-LCFAs appeared prominently in piglets exposed to high RVSP-to-left ventricular systolic pressure ratio and high RV rate-pressure product, an indicator of myocardial oxygen demand. Acute RVPO after CPB strongly inhibits LCFA oxidation without compensation by lactate oxidation, resulting in energy deficiency as determined by lower (phosphocreatine)/(adenosine triphosphate) in PAB-CPB. Adequate energy supply but also metabolic interventions may be required to circumvent these RV energy metabolic abnormalities during RVPO after CPB.

Sex differences in right ventricular adaptation to pressure overload in a rat model.

With severe right ventricular (RV) pressure overload, women demonstrate better clinical outcomes compared with men. The mechanoenergetic mechanisms underlying this protective effect, and their dependence on female endogenous sex hormones, remain unknown. To investigate these mechanisms and their impact on RV systolic and diastolic functional adaptation, we created comparable pressure overload via pulmonary artery banding (PAB) in intact male and female Wistar rats and ovariectomized (OVX) female rats. At 8 wk after surgery, right heart catheterization demonstrated increased RV energy input [indexed pressure-volume area (iPVA)] in all PAB groups, with the greatest increase in intact females. PAB also increased RV energy output [indexed stroke or external work (iEW)] in all groups, again with the greatest increase in intact females. In contrast, PAB only increased RV contractility-indexed end-systolic elastance (iEes)] in females. Despite these sex-dependent differences, no statistically significant effects were observed in the ratio of RV energy output to input (mechanical efficiency) or in mechanoenergetic cost to pump blood with pressure overload. These metrics were similarly unaffected by loss of endogenous sex hormones in females. Also, despite sex-dependent differences in collagen content and organization with pressure overload, decreases in RV compliance and relaxation time constant (tau Weiss) were not determined to be sex dependent. Overall, despite sex-dependent differences in RV contractile and fibrotic responses, RV mechanoenergetics for this degree and duration of pressure overload are comparable between sexes and suggest a homeostatic target.NEW & NOTEWORTHY Sex differences in right ventricular mechanical efficiency and energetic adaptation to increased right ventricular afterload were measured. Despite sex-dependent differences in contractile and fibrotic responses, right ventricular mechanoenergetic adaptation was comparable between the sexes, suggesting a homeostatic target.

Influence of right ventricular pressure and volume overload on right and left ventricular diastolic function.

BACKGROUND: Ventricular interdependence may account for altered ventricular mechanics in congenital heart disease. The present study aimed to identify differences in load-dependent right ventricular (RV)-left ventricular (LV) interactions in porcine models of pulmonary stenosis (PS) and pulmonary insufficiency (PI) by invasive admittance-derived hemodynamics in conjunction with noninvasive cardiovascular magnetic resonance (CMR). METHODS: Seventeen pigs were used in the study (7 with PS, 7 with PI, and 3 controls). Progressive PS was created by tightening a Teflon tape around the pulmonary artery, and PI was created by excising 2 leaflets of the pulmonary valve. Admittance catheterization data were obtained for the RV and LV at 10 to 12 weeks after model creation, with the animal ventilated under temporary diaphragm paralysis. CMR was performed in all animals immediately prior to pressure-volume catheterization. RESULTS: In the PS group, RV contractility was increased, manifested by increased end-systolic elastance (mean difference, 1.29 mm Hg/mL; 95% confidence interval [CI], 0.57-2.00 mm Hg/mL). However, in the PI group, no significant changes were observed in RV systolic function despite significant changes in RV diastolic function. In the PS group, LV end-systolic volume was significantly lower compared with controls (mean difference, 25.1 mL; 95% CI, -40.5 to -90.7 mL), whereas in the PI group, the LV showed diastolic dysfunction, demonstrated by an elevated isovolumic relaxation constant and ventricular stiffness (mean difference, 0.03 mL-1; 95% CI, -0.02 to 0.09 mL-1). CONCLUSIONS: The LV exhibits systolic dysfunction and noncompliance with PI. PS is associated with preserved LV systolic function and evidence of some LV diastolic dysfunction. Interventricular interactions influence LV filling and likely account for differential effects of RV pressure and volume overload on LV function.

Neuregulin-1 enhances cell-cycle activity, delays cardiac fibrosis, and improves cardiac performance in rat pups with right ventricular pressure load.

OBJECTIVES: Right ventricular (RV) failure is a leading cause of death in patients with congenital heart disease. RV failure is kept at bay during childhood. Limited proliferation of cardiomyocytes is present in the postnatal heart. We propose that cardiomyocyte proliferation improves RV adaptation to pressure load (PL). We studied adaptation in response to increased RV PL and the role of increased cardiomyocyte cell cycle activity (CCA) in rat pups growing into adulthood. METHODS: We induced RV PL at day of weaning in rats (3 weeks; 30-40 g) by pulmonary artery banding and followed rats into adulthood (300 g). We performed histological analyses and RNA sequencing analysis. To study the effects of increased cardiomyocyte cell cycle activity, we administered neuregulin-1 (NRG1), a growth factor involved in cardiac development. RESULTS: PL induced an increase in CCA, with subsequent decline of CCA (sham/PL at 4 weeks: 0.14%/0.83%; P = .04 and 8 weeks: 0.00%/0.00%; P = .484) and cardiac function (cardiac index: control/PL 4 weeks: 4.41/3.29; P = .468 and 8 weeks: 3.57/1.44; P = .024). RNA sequencing analysis revealed delayed maturation and increased CCA pathways. NRG1 stimulated CCA (PL vehicle/NRG1 at 2 weeks: 0.62%/2.28%; P = .003), improved cardiac function (cardiac index control vs vehicle/NRG1 at 2 weeks: 4.21 vs 3.07/4.17; P = .009/.705) and postponed fibrosis (control vs vehicle/NRG1 at 4 weeks: 1.66 vs 4.82%/2.97%; P = .009/.078) in RV PL rats during childhood. CONCLUSIONS: RV PL during growth induces a transient CCA increase. Further CCA stimulation improves cardiac function and delays fibrosis. This proof-of-concept study shows that stimulation of CCA can improve RV adaptation to PL in the postnatal developing heart and might provide a new approach to preserve RV function in patients with congenital heart disease.

Long-term Implications of Post-Procedural Left Ventricular End-Diastolic Pressure in Patients Undergoing Transcatheter Aortic Valve Implantation.

Current risk models have only limited accuracy in predicting transcatheter aortic valve Implantation (TAVI) outcomes and there is a paucity of clinical variables to guide patient management after the procedure. The prognostic impact of elevated left ventricular end-diastolic pressure (LVEDP) in TAVI patients is unknown. The aim of the present study was to evaluate the prognostic value of after-procedural LVEDP in patients who undewent TAVI. Consecutive patients with severe symptomatic aortic stenosis who undewent TAVI were divided into 2 groups according to after-procedural LVEDP above and below or equal 12 mm Hg. Collected data included baseline clinical, laboratory and echocardiographic variables. We evaluated the impact of elevated vs. normal LVEDP on in-hospital outcomes, short- and long-term mortality. Eight hundred forty-five patients were included in the study with complete in-hospital and late mortality data available for all survivors (median follow-up 29.5 months [IQR 16.5 to 48.0]). The mean age (±SD) was 82.3±6.2 years and mean Society of Thoracic Surgery score was 4.0%±3.0%. Patients with LVEDP>12 mm Hg (n = 591, 70%) and LVEDP≤12 mm Hg (n = 254, 30%) had a 6-months mortality rate of 6.8% and 2%, respectively (P=0.004) and a 1-year mortality rate of 10.1% vs 4.9%, respectively (p = 0.017). By multivariable analysis, after-procedural LVEDP>12 mm Hg was independently associated with all-cause mortality (HR 2.45, 95% CI 1.58 to 3.76, p <0.001) during long-term follow-up. In conclusion, elevated after-procedural LVEDP in patients who undewent TAVI is an independent predictor of mortality following TAVI. Further research regarding the use of LVEDP as a tool for after-procedural medical management is warranted.

Sustained Improvement in Diastolic Reserve Following Percutaneous Pericardiotomy in a Porcine Model of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence, but few effective treatments are available. Elevated left ventricular (LV) diastolic filling pressures represent a key therapeutic target. Pericardial restraint contributes to elevated LV end-diastolic pressure, and acute studies have shown that pericardiotomy attenuates the rise in LV end-diastolic pressure with volume loading. However, whether these acute effects are sustained chronically remains unknown. METHODS: Minimally invasive pericardiotomy was performed percutaneously using a novel device in a porcine model of heart failure with preserved ejection fraction. Hemodynamics were assessed at baseline and following volume loading with pericardium intact, acutely following pericardiotomy, and then again chronically after 4 weeks. Cardiac structure was assessed by magnetic resonance imaging. RESULTS: The increase in LV end-diastolic pressure with volume loading was mitigated by 41% (95% CI, 27%-45%, P<0.0001; ΔLV end-diastolic pressure reduced from +9±3 mm Hg to +5±3 mm Hg, P=0.0003, 95% CI, -2.2 to -5.5). The effect was sustained at 4 weeks (+5±2 mm Hg, P=0.28 versus acute). There was no statistically significant effect of pericardiotomy on ventricular remodeling compared with age-matched controls. None of the animals developed hemodynamic or pathological indicators of pericardial constriction or frank systolic dysfunction. CONCLUSIONS: The acute hemodynamic benefits of pericardiotomy are sustained for at least 4 weeks in a swine model of heart failure with preserved ejection fraction, without excessive chamber remodeling, pericarditis, or clinically significant systolic dysfunction. These data support trials evaluating minimally invasive pericardiotomy as a novel treatment for heart failure with preserved ejection fraction in humans.

Left ventricular filling pressure and survival following aortic valve replacement for severe aortic stenosis.

OBJECTIVE: To determine whether echocardiography-derived left ventricular filling pressure influences survival in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). METHODS: We retrospectively reviewed 1383 consecutive patients with severe AS, normal ejection fraction and interpretable filling pressure undergoing AVR. Left ventricular filling pressure was determined according to current guidelines using mitral inflow, mitral annular tissue Doppler, estimated right ventricular systolic pressure and left atrial volume index. Cox proportional hazards regression was used to assess the influence of various parameters on mortality. RESULTS: Age was 75±10 years and 552 (40%) were female. Left ventricular filling pressure was normal in 325 (23%), indeterminate in 463 (33%) and increased in 595 (43%). Mean follow-up was 7.3±3.7 years, and mortality was 1.2%, 4.2% and 18.9% at 30 days and 1 and 5 years, respectively. Compared with patients with normal filling pressure, patients with increased filling pressure were older (78±9 vs 70±12, p<0.001), more often female (45% vs 35%, p=0.002) and were more likely to have New York Heart Association class III-IV symptoms (35% vs 24%, p=0.004), coronary artery disease (55% vs 42%, p<0.001) and concentric left ventricular hypertrophy (63% vs 37%, p<0.001). After correction for other factors, increased left ventricular filling pressure remained an independent predictor of mortality after successful AVR (adjusted HR 1.45 (95% CI 1.16 to 1.81), p=0.005). CONCLUSIONS: Preoperative increased left ventricular filling pressure is common in patients with AS undergoing AVR and has important prognostic implications, regardless of symptom status. Future prospective studies should consider whether patients with increased filling pressure would benefit from earlier operation.

Transcatheter aortic valve replacement acutely improves left ventricular mechanical efficiency in severe aortic stenosis: effects of different phenotypes.

AIM: Aortic stenosis is a frequent valvular disease, with transcatheter aortic valve implantation (TAVI) being performed when surgical replacement is at increased risk. However, TAVI-induced effects on myocardial efficiency are unknown. We aimed to investigate changes in LV mechano-energetic pre-/post-TAVI and their prognostic impact. METHODS: A total of 46 patients (25 males) received transesophageal and simultaneous radial pressure plus transaortic gradient monitoring before/immediately after prosthesis deployment. Efficiency was computed as external work/potential energy, as derived from LV pressure-volume plots; myocardial oxygen consumption (MVO2) was estimated as PWImod, i.e. a noninvasively validated alternative for MVO2 estimation. RESULTS: TAVI was successful in all patients, peak transaortic gradient decreasing - 40 ± 20 mmHg (p < 0.001). Efficiency improved post-TAVI (+ 0.6 ± 0.12; p = 0.004), with a concomitant PWImod reduction (- 16 ± 31%; p < 0.001). When contextualized to fixed PWImod value (5 ml/min/100 g), efficiency significantly affected survival (p = 0.029). Over 1026 ± 450-day follow-up, a change in efficiency pre-/post-TAVI ≤ 0.021 (median of the difference) predicted more deaths from any cause (30%) as compared with a change > 0.021 (17%), particularly in those patients with a pre-TAVI mean high-gradient (HG ≥ 40 mmHg) phenotype (p < 0.05). In particular, HG patients exhibited the lowest efficiency/PWImod ratio pre-/post-TAVI (p = 0.048), relative to the other aortic stenosis patients, suggestive of an unfavourable matching between cardiac function and metabolic demand, which foreshortens some intrinsic damaged muscle condition in these patients. CONCLUSION: LV mechanical efficiency improves immediately post-TAVI, notwithstanding an inhomogeneous mechano-energetic matching among the aortic stenosis patients, which can impact negatively on their long-term prognosis, particularly in those with the HG phenotype.

Intraoperative measurement of intraventricular pressure in dogs with communicating internal hydrocephalus.

Collapse of the lateral cerebral ventricles after ventriculo-peritoneal drainage is a fatal complication in dogs with internal hydrocephalus. It occurs due to excessive outflow of cerebrospinal fluid into the peritoneal cavity (overshunting). In most shunt systems, one-way valves with different pressure settings regulate flow into the distal catheter to avoid overshunting. The rationale for the choice of an appropriate opening pressure is a setting at the upper limit of normal intracranial pressure in dogs. However, physiological intraventricular pressure in normal dogs vary between 5 and 12 mm Hg. Furthermore, we hypothesise that intraventricular pressure in hydrocephalic dogs might differ from pressure in normal dogs and we also consider that normotensive hydrocephalus exists in dogs, as in humans. In order to evaluate intraventricular pressure in hydrocephalic dogs, twenty-three client owned dogs with newly diagnosed communicating internal hydrocephalus were examined before implantation of a ventriculo-peritoneal shunt using a single use piezo-resistive strain-gauge sensor (MicroSensor ICP probe). Ventricular volume and brain volume were measured before surgery, based on magnetic resonance images. Total ventricular volume was calculated and expressed in relation to the total volume of the brain, including the cerebrum, cerebellum, and brainstem (ventricle-brain index). Multiple logistic regression analysis was performed to assess the influence of the covariates "age", "gender", "duration of clinical signs", "body weight", and "ventricle-brain index" on intraventricular pressure. The mean cerebrospinal fluid pressure in the hydrocephalic dogs was 8.8 mm Hg (standard deviation 4.22), ranging from 3-18 mm Hg. The covariates "age", (P = 0.782), "gender" (P = 0.162), "body weight", (P = 0.065), or ventricle-brain index (P = 0.27)" were not correlated with intraventricular pressure. The duration of clinical signs before surgery, however, was correlated with intraventricular pressure (P< 0.0001). Dogs with internal hydrocephalus do not necessarily have increased intraventricular pressure. Normotensive communicating hydrocephalus exists in dogs.

Extubation on the operating table in patients with right ventricular pressure overload undergoing biventricular repair†.

OBJECTIVES: Right ventricular pressure overload, which can result in restrictive right ventricular physiology, predicts slow recovery after biventricular repair of congenital heart defects. The goal of the study was to assess how extubation in the operating room influences the postoperative course in these patients. METHODS: Between January 2013 and June 2017, a total of 65 children [median age 0.96 (0.13-9.47) years; median weight 8 (3.05-25.8) kg] with right ventricular pressure overload underwent an intracardiac correction. The most common malformations were tetralogy of Fallot (n = 34) and double outlet right ventricle with pulmonary stenosis (n = 11). The patients were divided into 2 groups: the first (n = 36) comprised late extubated (LE) and the second (n = 29), early extubated (EE) children, immediately after chest closure in the operating room. Preoperative, perioperative and postoperative records were analysed retrospectively. RESULTS: Children who had EE had a lower heart rate (EE 124.2 vs LE 133.6 bpm; P = 0.03), higher arterial blood pressure (systolic: EE 87.9 ± 9.35 vs LE 81.4 ± 12.0 mmHg; P = 0.029; diastolic: EE 51.1 ± 6.5 vs LE 45.9 ± 6.64 mmHg; P = 0.003), lower central venous pressure (EE 8.6 ± 1.89 mmHg vs LE 9.9 ± 2.42 mmHg; P = 0.03), fewer pleural effusions in the first 6 postoperative days (EE 1.38 ml/kg/day vs LE 5.98 ml/kg/day; P = 0.009), shorter time of dopamine support ≥3 µg/kg (EE 7.29 ± 12.26 h vs LE 34.78 ± 38.05 h, P < 0.001), shorter stays in the intensive care unit (EE 2.7 ± 2.67 vs LE 5.0 ± 4.77 days, P = 0.001) and hospital (EE 11.8 ± 4.79 vs LE 15.5 ± 7.8 days; P = 0.022). CONCLUSIONS: Extubation in the operating room of children with right ventricular pressure overload undergoing biventricular correction is feasible and safe and has a beneficial effect on the postoperative course.

Impact of High Baseline Left Ventricular Filling Pressure on Transcatheter Aortic Valve Replacement Outcomes in Patients with Significant Mitral Annular Calcification.

BACKGROUND: Left ventricular filling pressure (LVFP) has been demonstrated to be a major predictor of poor cardiovascular outcomes. However, estimation of LVFP in patients with aortic stenosis is limited by the high prevalence of significant mitral annular calcification. The aim of this study was to investigate the effect of transcatheter aortic valve replacement on LVFP and the relationship of LVFP to mortality and hospitalization. METHODS: This was a single-center, retrospective study of 140 consecutive patients in sinus rhythm with significant mitral annular calcification who underwent transcatheter aortic valve replacement for severe aortic stenosis from May 2011 to June 2015. Mean follow-up duration was 3.06 ± 1.48 years (minimum, 2.4 years; maximum, 6.5 years). Diastolic function was assessed using recently proposed criteria for those with significant mitral annular calcification. High LVFP was defined as a mitral E/A ratio > 1.8 or a ratio of 0.8 to 1.8 and isovolumic relaxation time < 80 msec. RESULTS: At baseline, the proportion of patients with high LVFP was 40.7%, similar to 1 month (39.7%) (P = .86). However, the proportion of patients with high LVFP was significantly decreased at 1 year compared with those at baseline (26.9% vs 40.7%, P = .02). Multivariate analysis showed that high LVFP at baseline significantly increased risk for all-cause mortality compared with patients with normal LVFP (hazard ratio, 2.84; 95% confidence interval, 1.33-6.05; P = .007). CONCLUSIONS: High baseline LVFP was associated with a significantly increased all-cause mortality, and LVFP does not improve in the short term but only at 1 year after transcatheter aortic valve replacement.

Right ventricular pressure overload alters cardiac lipid composition.

INTRODUCTION: Right ventricular (RV) failure due to pressure load is an important determinant of clinical outcome in pulmonary hypertension, congenital heart disease and left ventricular failure. The last decades it has become clear that metabolic dysregulation is associated with the development of RV-failure. However, underlying mechanisms remain to be unraveled. Recently, disruption of intracardiac lipid content has been suggested as potential inducer of RV failure. In the present study, we used a rat model of RV-dysfunction and aimed to obtain insight in temporal changes in RV-function, -remodelling and -metabolism and relate this to RV lipid content. METHODS AND RESULTS: Male Wistar WU rats were subjected to pulmonary artery banding (n = 25) or sham surgery (n = 14) and cellular, hemodynamic and metabolic assessments took place after 2, 5 and 12 weeks. In this model RV dysfunction and remodelling occurred, including early upregulation of oxidative stress markers. After 12 weeks of pressure load, lipidomics revealed significant decreases of myocardial diglycerides and cardiolipins, driven by (poly-)unsaturated forms. The decrease of cardiolipins was driven by its most abundant form, tetralinoleoylcardiolipin. Mitochondrial capacity for fatty acid oxidation preserved, while the capacity for glucose oxidation increased. CONCLUSION: RV dysfunction due to pressure load, is associated with decreased intracardiac unsaturated lipids, especially tetralinoleoylcardiolipin. This was accompanied with preserved mitochondrial capacity regarding fatty acids oxidation, with increased capacity for glucose oxidation, and early activation of oxidative stress. We suggest that early interventions should be directed towards preservation of lipid availability as possible mean in order to prevent RV failure.

Serial Measurements of Left Ventricular Systolic and Diastolic Function by Cardiac Magnetic Resonance Imaging in Patients with Early Stage Breast Cancer on Trastuzumab.

Our aim was to evaluate the temporal changes in left ventricular (LV) diastolic filling in relation to other LV parameters using cardiac MRI (CMR) in patients with HER2 positive breast cancer receiving trastuzumab therapy. Fourty-one women with early stage HER2+ breast cancer underwent serial CMR (baseline, 6, 12, and 18 months) after initiation of trastuzumab therapy. A single, blinded observer measured LV parameters on de-identified CMRs in random order. Linear mixed models were used to investigate temporal changes. Compared to baseline, there were significant decreases in systolic function as measured by both left ventricular ejection fraction (LVEF) (p <0.001 at 6 and 12 months) and peak ejection rate corrected for end-diastolic volume (PER/LVEDV) (p = 0.008 at 6 months, p = 0.01 at 12 months). However, these differences were no longer significant at 18 months. In contrast, significant reductions in diastolic function as measured by LV peak filling rate corrected for end-diastolic volume (PFR/LVEDV) were observed at 6 months (p = 0.012), 12 months (p = 0.031), and up to 18 months (p = 0.034). There were no significant temporal changes in the time to peak filling rate corrected for cardiac cycle (TPF/RR). The reduction in PFR/LVEDV at 18 months was no longer significant when corrected for heart rate. In conclusion, there were significant subclinical deleterious effects on both LV systolic and diastolic function among patients receiving trastuzumab. While there was recovery in LV systolic function after therapy cessation at 18 months, reduction in PFR/LVEDV appeared to persist. Thus, diastolic dysfunction may serve as a marker of trastuzumab-induced cardiotoxicity that needs to be confirmed in a larger study.

Perioperative Right Ventricular Pressure Monitoring in Cardiac Surgery.

Right ventricular (RV) dysfunction is a cause of increased morbidity and mortality in both cardiac surgery and noncardiac surgery and in the intensive care unit. Early diagnosis of this condition still poses a challenge. The diagnosis of RV dysfunction traditionally is based on a combination of echocardiography, hemodynamic measurements, and clinical symptoms. This review describes the method of using RV pressure waveform analysis to diagnose and grade the severity of RV dysfunction. The authors describe the technique, optimal use, and pitfalls of this method, which has been used at the Montreal Heart Institute since 2002, and review the current literature on this method. The RV pressure waveform is obtained using a pulmonary artery catheter with the capability of measuring RV pressure by connecting a pressure transducer to the pacemaker port. The authors describe how RV pressure waveform analysis can facilitate the diagnosis of systolic and diastolic RV dysfunction, the evaluation of RV-arterial coupling, and help diagnose RV outflow tract obstruction. RV pressure waveform analysis also can be used to guide pharmacologic treatment and fluid resuscitation strategies for RV dysfunction.

Perioperative Echocardiographic Index of Left Ventricular Filling Pressure in Cardiac Surgery.

BACKGROUND: The elevated preoperative ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e') as an echocardiographic index of left ventricular filling pressure is known to be associated with poor postoperative outcomes. We investigated the association between preoperative and postoperative E/e' elevation and clinical outcomes after cardiac operations. METHODS: The study divided 1,353 patients who underwent cardiac operations into four groups: preoperative and postoperative E/e' ≤15 (low-low), preoperative E/e' ≤15 but postoperative E/e' >15 (low-high), preoperative E/e' >15 but postoperative E/e' ≤15 (high-low), and preoperative and postoperative E/e' >15 (high-high). Cox proportional hazard analysis was performed. Kaplan-Meier curve analysis was performed before and after propensity score matching. RESULTS: The four perioperative E/e' categories were independently associated with 5-year mortality (hazard ratio, high-high vs low-low: 3.58; low-high vs low-low: 3.75; high-low vs low-low: 1.18). Kaplan-Meier curves showed that mortality was significantly different between the groups (log-rank test: high-high vs. low-low, p < 0.001; low-high vs low-low, p < 0.001). Postoperative intensive care unit and hospital lengths of stay, incidence of acute kidney injury, and 1-year mortality were significantly different. However, after propensity score matching, mortality and the incidence of postoperative acute kidney injury were significantly different only between postoperative E/e' ≤15 and E/e' >15, but not between preoperative E/e' ≤15 and E/e' >15. CONCLUSIONS: Postoperative E/e' >15 was more strongly associated with mortality and acute kidney injury than preoperative E/e' >15. Measurement of the postoperative E/e' ratio may help in assessing the risk of these patients.

Left Ventricular Function After Repair of Totally Anomalous Pulmonary Venous Connection.

BACKGROUND: Poor left ventricular (LV) growth and diastolic dysfunction long after simple total anomalous pulmonary venous connection (TAPVC) repair has been well documented and is believed to originate from insufficient preoperative volume preload. The objective of the study was to confirm these findings. METHODS: Of 61 patients undergoing simple TAPVC repair between 1996 and 2016, 42 patients undergoing postoperative catheter examinations were enrolled. The mean age at the time of repair was 39 ± 117 days. Postoperative catheter examinations were conducted at a mean duration of 1.1 years after the repair. LV end-diastolic volume (LVEDV) was calculated by biplane cineangiography with the use of Simpson's method as a Graham modification. RESULTS: LV ejection fraction, LV end-diastolic pressure (LVEDP), and cardiac index were 72% ± 5%, 10.3 ± 2.7 mm Hg, and 4.0 ± 0.7 L •·min-1 • m-2, respectively. LVEDV was 102% ± 16% of the predictive normal value, and it strongly correlated with the predictive normal value of LV end-diastolic diameter (LVEDd) calculated by two-dimensional echocardiography (R2 = 0.29, p = 0.005). LVEDd maintained a normal range thereafter during the entire follow-up period. LVEDP correlated linearly with age at the time of TAPVC repair (R2 = 0.18, p = 0.007) but not with LVEDV (p = 0.67). CONCLUSIONS: LV size maintained a normal range after the repair of simple TAPVC. High LVEDP was frequently observed a year after repair; it did not correlate with LV size but had a strong negative correlation with age at the time of repair.

Independent of left ventricular mass, circulating inflammatory markers rather than pressure load are associated with concentric left ventricular remodelling.

BACKGROUND: A reason for concentric left ventricular (LV) remodelling predicting cardiovascular outcomes independent of conventional risk factors and LV mass (LVM) has not been provided. We hypothesized that independent of LVM, concentric LV remodelling is associated with inflammatory changes rather than a pressure load on the LV. METHODS: In 764 randomly selected community participants, we assessed relations between several inflammatory markers (ELISA) and LV relative wall thickness (RWT) (echocardiography), LV mass index (LVMI), and indexes of diastolic function. RESULTS: No independent relations were noted between circulating concentrations of inflammatory markers and LVM index (LVMI) (p > 0.13 for all). However, independent of confounders including LVMI and blood pressure (BP), circulating tumour necrosis factor-α (TNF-α) (partial r = 0.14, p < 0.0005) and to a lesser degree interleukin-6 (partial r = -0.09, p < 0.02) were associated with RWT. The impact (standardized ß-coefficient) of TNF-α on RWT (0.12 ±â€¯0.03, p < 0.0005) was at least as strong as age (0.13 ±â€¯0.05, p < 0.005), and second only to LVMI (0.27 ±â€¯0.04, p < 0.0001), whilst neither office, 24-hour, central aortic BP, nor aortic stiffness were associated with RWT independent of LVMI. With adjustments, as compared to participants with a normal LVMI and geometry (12.7 ±â€¯0.8), circulating TNF-α concentrations (pg/ml) were increased as much in participants with concentric LV remodelling (16.8 ±â€¯1.5, p < 0.05) as in those with concentric LV hypertrophy (LVH) (17.0 ±â€¯1.3, p < 0.005), whilst eccentric LVH (13.7 ±â€¯0.9) was not. No independent relations between inflammatory markers and LV diastolic function (trans-mitral and tissue Doppler) were noted. CONCLUSIONS: Independent of LVMI, a pro-inflammatory state rather than BP load is strongly associated with LV concentric remodelling.

Stent angioplasty of narrowed right ventricular outflow conduits and pulmonary arteries consistently reduces right ventricular systolic pressures and delays subsequent surgeries.

OBJECTIVES: Narrowed right ventricular (RV) outflow conduits and pulmonary arteries (PA) increase RV pressures and warrant interventions. Stent angioplasty is an alternative to more morbid redo-surgery in developing countries. We evaluate the efficacy and safety of stenting and assess need for redo-surgical reinterventions on midterm follow-up after stent angioplasty. METHODS: Patients who underwent conduit, main PA and bilateral branch PA stenting for elevated RV pressures were analyzed retrospectively. Success was defined as 20% reduction in RV pressures or RV-aortic pressure ratio; 50% reduction in gradients or 50% increase of luminal diameter. Procedural results, complications and need for redo surgeries on follow-up were assessed. RESULTS: Among 60 patients aged 1-46years, 57 were post-operative patients, who needed stenting at a median period of 48 months after surgery. Stenting succeeded in 98% and reduced RV pressures from 105.42±28.39mmHg to 54.46±16.89mmHg. Direct major procedural complications in five (8%) patients included procedural failure in one, stent migration in three and lung hemorrhage in one. None of the stented conduits needed a surgical change on a follow-up ranging 3-120 months. Following bilateral PA stenting in twenty-four patients, only two needed a repeat open-heart surgery during follow-up ranging 3-108 months. Catheter reinterventions on follow-up included elective percutaneous pulmonary valve implantation in nine patients and stent redilation in seven patients. CONCLUSIONS: Stent angioplasty was safe and effective. Surgery was postponed in all stenosed conduits. Elective redilation of stents after bilateral PA stenting may be needed for somatic growth; but open-heart repeat surgeries can be avoided in a majority.