Unloading the Left Ventricle in Venoarterial ECMO: In Whom, When, and How?

Venoarterial extracorporeal membrane oxygenation provides cardiorespiratory support to patients in cardiogenic shock. This comes at the cost of increased left ventricle (LV) afterload that can be partly ascribed to retrograde aortic flow, causing LV distension, and leads to complications including cardiac thrombi, arrhythmias, and pulmonary edema. LV unloading can be achieved by using an additional circulatory support device to mitigate the adverse effects of mechanical overload that may increase the likelihood of myocardial recovery. Observational data suggest that these strategies may improve outcomes, but in whom, when, and how LV unloading should be employed is unclear; all techniques require balancing presumed benefits against known risks of device-related complications. This review summarizes the current evidence related to LV unloading with venoarterial extracorporeal membrane oxygenation.

Cardiogenic shock in pregnancy.

Cardiac disease complicates 1%-4% of pregnancies globally, with a predominance in low and middle-income countries (LMICs). Increasing maternal age, rates of obesity, cardiovascular comorbidities, pre-eclampsia and gestational diabetes all contribute to acquired cardiovascular disease in pregnancy. Additionally, improved survival in congenital heart disease (CHD) has led to increasing numbers of women with CHD undergoing pregnancy. Implementation of individualised care plans formulated through pre-conception counselling and based on national and international guidance have contributed to improved clinical outcomes. However, there remains a significant proportion of women of reproductive age with no apparent comorbidities or risk factors that develop heart disease during pregnancy, with no indication for pre-conception counselling. The most extreme manifestation of cardiac disease is cardiogenic shock (CS), where the primary cardiac pathology results in inadequate cardiac output and hypoperfusion, and is associated with significant mortality and morbidity. Key to management is early recognition, intervention to treat any potentially reversible underlying pathology and supportive measures, up to and including mechanical circulatory support (MCS). In this narrative review we discuss recent developments in the classification of CS, and how these may be adapted to improve outcomes of pregnant women with, or at risk of developing, this potentially lethal condition.

Competency-based cardiac imaging for patient-centred care. A statement of the European Society of Cardiology (ESC). With the contribution of the European Association of Cardiovascular Imaging (EACVI), and the support of the Association of Cardiovascular Nursing & Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), the European Association of Preventive Cardiology (EAPC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Heart Rhythm Association (EHRA), and the Heart Failure Association (HFA) of the ESC.

Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology-with specific adaptations to imaging of the heart-as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care.

Mechanical circulatory support in the treatment of cardiogenic shock.

PURPOSE OF REVIEW: Cardiogenic shock is a condition that is characterized by end-organ hypoperfusion secondary to reduced cardiac output, and is associated with substantial mortality. The mainstay of therapy for cardiogenic shock is reversal of the underlying cause, and concomitant supportive care with vasoactive medications (vasopressors and inotropes). Patients who continue to deteriorate despite these measures may require mechanical circulatory support (MCS). Here, we review the devices available for MCS, and their associated benefits and risks. RECENT FINDINGS: Despite growing use worldwide, there is little randomized evidence supporting the routine use of any specific device for MCS in cardiogenic shock. A large randomized trial of the intra-aortic balloon pump did not demonstrate short- or long-term improvement in mortality. The TandemHeart and Impella devices which assist in left ventricular unloading have only been evaluated in small randomized trials, which showed an increase in adverse events without improvement in mortality. Finally, venoarterial extracorporeal membrane oxygenation (provides both circulatory and respiratory support) and is currently being evaluated in large randomized clinical trials. SUMMARY: Various devices for MCS in cardiogenic shock are available, but routine use is not supported by high-quality randomized evidence. Given the resources required for initiation of MCS, use of these treatments should be limited to centers experienced in advanced cardiac care, and future research should focus on what role (if any) these devices have in clinical practice.

Managing Harlequin Syndrome in VA-ECMO - do not forget the right ventricle.

Harlequin Syndrome (also known as North-South Syndrome) is a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) that can occur when left ventricular function starts to recover. While most commonly due to continued impaired gas exchange in the lungs, we present a case caused by right ventricular dysfunction, successfully managed by conversion of the ECMO circuit to a veno-veno-arterial (VV-A) configuration.

Temporary circulatory support for cardiogenic shock.

Cardiogenic shock can occur due to acute ischaemic or non-ischaemic cardiac events, or from progression of long-standing underlying heart disease. When addressing the cause of underlying disease, the management of cardiogenic shock consists of vasopressors and inotropes; however, these agents can increase myocardial oxygen consumption, impair tissue perfusion, and are frequently ineffective. An alternative approach is to temporarily augment cardiac output using mechanical devices. The use of these devices-known as temporary circulatory support systems-has increased substantially in recent years, despite being expensive, resource intensive, associated with major complications, and lacking high-quality evidence to support their use. This Review summarises the physiological basis underlying the use of temporary circulatory support for cardiogenic shock, reviews the evidence informing indications and contraindications, addresses ethical considerations, and highlights the need for further research.

Prevalence of Thrombotic Complications in ICU-Treated Patients With Coronavirus Disease 2019 Detected With Systematic CT Scanning.

OBJECTIVES: Severe coronavirus disease 2019 is associated with an extensive pneumonitis and frequent coagulopathy. We sought the true prevalence of thrombotic complications in critically ill patients with severe coronavirus disease 2019 on the ICU, with or without extracorporeal membrane oxygenation. DESIGN: We undertook a single-center, retrospective analysis of 72 critically ill patients with coronavirus disease 2019-associated acute respiratory distress syndrome admitted to ICU. CT angiography of the thorax, abdomen, and pelvis were performed at admission as per routine institution protocols, with further imaging as clinically indicated. The prevalence of thrombotic complications and the relationship with coagulation parameters, other biomarkers, and survival were evaluated. SETTING: Coronavirus disease 2019 ICUs at a specialist cardiorespiratory center. PATIENTS: Seventy-two consecutive patients with coronavirus disease 2019 admitted to ICU during the study period (March 19, 2020, to June 23, 2020). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All but one patient received thromboprophylaxis or therapeutic anticoagulation. Among 72 patients (male:female = 74%; mean age: 52 ± 10; 35 on extracorporeal membrane oxygenation), there were 54 thrombotic complications in 42 patients (58%), comprising 34 pulmonary arterial (47%), 15 peripheral venous (21%), and five (7%) systemic arterial thromboses/end-organ embolic complications. In those with pulmonary arterial thromboses, 93% were identified incidentally on first screening CT with only 7% suspected clinically. Biomarkers of coagulation (e.g., d-dimer, fibrinogen level, and activated partial thromboplastin time) or inflammation (WBC count, C-reactive protein) did not discriminate between patients with or without thrombotic complications. Fifty-one patients (76%) survived to discharge; 17 (24%) patients died. Mortality was significantly greater in patients with detectable thrombus (33% vs 10%; p = 0.022). CONCLUSIONS: There is a high prevalence of thrombotic complications, mainly pulmonary, among coronavirus disease 2019 patients admitted to ICU, despite anticoagulation. Detection of thrombus was usually incidental, not predicted by coagulation or inflammatory biomarkers, and associated with increased risk of death. Systematic CT imaging at admission should be considered in all coronavirus disease 2019 patients requiring ICU.

Perioperative management of patients with pulmonary hypertension undergoing non-cardiothoracic, non-obstetric surgery: a systematic review and expert consensus statement.

BACKGROUND: The risk of complications, including death, is substantially increased in patients with pulmonary hypertension (PH) undergoing anaesthesia for surgical procedures, especially in those with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). Sedation also poses a risk to patients with PH. Physiological changes including tachycardia, hypotension, fluid shifts, and an increase in pulmonary vascular resistance (PH crisis) can precipitate acute right ventricular decompensation and death. METHODS: A systematic literature review was performed of studies in patients with PH undergoing non-cardiac and non-obstetric surgery. The management of patients with PH requiring sedation for endoscopy was also reviewed. Using a framework of relevant clinical questions, we review the available evidence guiding operative risk, risk assessment, preoperative optimisation, and perioperative management, and identifying areas for future research. RESULTS: Reported 30 day mortality after non-cardiac and non-obstetric surgery ranges between 2% and 18% in patients with PH undergoing elective procedures, and increases to 15-50% for emergency surgery, with complications and death usually relating to acute right ventricular failure. Risk factors for mortality include procedure-specific and patient-related factors, especially markers of PH severity (e.g. pulmonary haemodynamics, poor exercise performance, and right ventricular dysfunction). Most studies highlight the importance of individualised preoperative risk assessment and optimisation and advanced perioperative planning. CONCLUSIONS: With an increasing number of patients requiring surgery in specialist and non-specialist PH centres, a systematic, evidence-based, multidisciplinary approach is required to minimise complications. Adequate risk stratification and a tailored-individualised perioperative plan is paramount.

Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review.

A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p < 0.001). Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU. Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.

Pulmonary Angiopathy in Severe COVID-19: Physiologic, Imaging, and Hematologic Observations.

Rationale: Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology.Objectives: To ascertain the physiologic, hematologic, and imaging basis of lung injury in severe COVID-19 pneumonia.Methods: Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography [n = 39] and dual-energy CT [DECT, n = 20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography.Measurements and Results: In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr [range, 29-79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H2O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic "shutdown". The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]) were present in all patients (wedge-shaped, n = 3; mottled, n = 9; mixed pattern, n = 6).Conclusions: Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.

COVID-19 Pulmonary Failure and Extracorporeal Membrane Oxygenation: First Experience from Three European Extracorporeal Membrane Oxygenation Centers.

On April 17, 2020, a coronavirus disease 2019 (COVID-19) webinar was held by selected international experts in the field of intensive care and specialized respiratory ECMO centers from Germany, Italy, Spain, and the United Kingdom, which was hosted by the German Heart Centre Berlin/Charité. The experts shared their experience about the treatment of 42 patients with severe acute respiratory failure requiring venovenous extracorporeal membrane oxygenation (VV-ECMO). Patients were predominantly male (male-to-female ratio: 3:1), with a mean age of 51 years (range: 25-73 years). VV-ECMO support was indicated in 30% of the ventilated COVID-19 patients. The mean time requiring mechanical ventilation was 16.5 days, with a mean duration of ECMO support of 10.6 days. At the time of the webinar, a total of 17 patients had already been decannulated from ECMO, whereas six died with multiorgan failure. 18 patients remained on ECMO, with their final outcomes unknown at the time of the webinar. Hospital mortality was 25.6% (as of April 17, 2020). In this respect, VV-ECMO, provided by expert centers, is a recognized and validated mode of advanced life-support during the recent COVID-19 pandemic with good outcomes.

Right ventricular time intervals - Comparison between pulsed wave Doppler and tissue Doppler imaging.

BACKGROUND: Cardiac time intervals are used as indices of systolic and diastolic function. Echocardiographic assessment of these intervals is based on either pulsed wave Doppler (PWD) or tissue Doppler imaging (TDI). We investigated the agreement between the two techniques in the evaluation of right ventricular (RV) time intervals in healthy adults. METHODS: In 123 healthy volunteers we used both PWD and TDI to assess RV time intervals (filling time - RVFT, ejection time - RVET), heart rate-corrected intervals (total filling time - t-FT, total ejection time - t-ET) and RV performance indices (total isovolumic time - t-IVT, myocardial performance index - MPI). Intraclass correlation coefficient (ICC) and Pearson analysis (r coefficient) were used to evaluate the agreement and correlation between the two techniques. RESULTS: PWD and TDI had excellent agreement and correlation in measuring RVFT (ICC 0.94 [95% CI 0.85 - 0.97], r 0.91) whereas a good agreement was found for RVET (ICC 0.63[95% CI - 0.14 - 0.84]; r 0.68). Good agreement and strong correlation were found for both t-FT (ICC 0.67 [95% CI 0.36 - 0.82]; r 0.59) and t-ET (ICC 0.71 [95% CI - 0.06-0.88]; r 0.74). The two methods had lower agreement in assessing RV t-IVT (ICC 0.52 [95% CI 0.3187-0.6622]; r 0.57) and MPI (ICC 0.36 [95% CI - 0.05-0.43]; r 0.50). CONCLUSION: In healthy adults, PWD and TDI are interchangeable in measuring RVFT, RVET, RV t-FT and RV t-ET. Lower agreement between the two techniques was found for RV t-IVT and MPI.

Intensive care unit management of percutaneous mechanical circulatory supported patients: the role of imaging.

The clinical management of patients on Impella support requires multimodality monitoring and imaging. Upon intensive care unit admission, echocardiography is essential to ensure correct pump positioning/guide repositioning, to monitor acute myocardial infarction/device-related cardiac complications and to evaluate baseline left and right ventricular function. Over time, the echocardiographic assessment of myocardial viability has become an essential target for guiding mechanical circulatory support escalation and long-term strategies. The recognition and grading of any valvular dysfunction and damage in Impella patients are challenging, as the device interferes with the colour Doppler signal, and the loading conditions of the left ventricle are modified by the pump. Valvular disease in such patients is often secondary, and correct identification is pivotal for future therapeutic strategies. The emerging use of newer techniques, including speckle-tracking echocardiography, is of increasing interest in the imaging of critically ill patients.

EAPCI Position Statement on Invasive Management of Acute Coronary Syndromes during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to healthcare worldwide. The infection can be life threatening and require intensive care treatment. The transmission of the disease poses a risk to both patients and healthcare workers. The number of patients requiring hospital admission and intensive care may overwhelm health systems and negatively affect standard care for patients presenting with conditions needing emergency interventions. This position statements aims to assist cardiologists in the invasive management of acute coronary syndrome (ACS) patients in the context of the COVID-19 pandemic. To that end, we assembled a panel of interventional cardiologists and acute cardiac care specialists appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and from the Acute Cardiovascular Care Association (ACVC) and included the experience from the first and worst affected areas in Europe. Modified diagnostic and treatment algorithms are proposed to adapt evidence-based protocols for this unprecedented challenge. Various clinical scenarios, as well as management algorithms for patients with a diagnosed or suspected COVID-19 infection, presenting with ST- and non-ST-segment elevation ACS are described. In addition, we address the need for re-organization of ACS networks, with redistribution of hub and spoke hospitals, as well as for in-hospital reorganization of emergency rooms and cardiac units, with examples coming from multiple European countries. Furthermore, we provide a guidance to reorganization of catheterization laboratories and, importantly, measures for protection of healthcare providers involved with invasive procedures.

Contemporary Presentation and Management of Valvular Heart Disease: The EURObservational Research Programme Valvular Heart Disease II Survey.

BACKGROUND: Valvular heart disease (VHD) is an important cause of mortality and morbidity and has been subject to important changes in management. The VHD II survey was designed by the EURObservational Research Programme of the European Society of Cardiology to analyze actual management of VHD and to compare practice with guidelines. METHODS: Patients with severe native VHD or previous valvular intervention were enrolled prospectively across 28 countries over a 3-month period in 2017. Indications for intervention were considered concordant if the intervention was performed or scheduled in symptomatic patients, corresponding to Class I recommendations specified in the 2012 European Society of Cardiology and in the 2014 American Heart Association/American College of Cardiology VHD guidelines. RESULTS: A total of 7247 patients (4483 hospitalized, 2764 outpatients) were included in 222 centers. Median age was 71 years (interquartile range, 62-80 years); 1917 patients (26.5%) were ≥80 years; and 3416 were female (47.1%). Severe native VHD was present in 5219 patients (72.0%): aortic stenosis in 2152 (41.2% of native VHD), aortic regurgitation in 279 (5.3%), mitral stenosis in 234 (4.5%), mitral regurgitation in 1114 (21.3%; primary in 746 and secondary in 368), multiple left-sided VHD in 1297 (24.9%), and right-sided VHD in 143 (2.7%). Two thousand twenty-eight patients (28.0%) had undergone previous valvular intervention. Intervention was performed in 37.0% and scheduled in 26.8% of patients with native VHD. The decision for intervention was concordant with Class I recommendations in symptomatic patients with severe single left-sided native VHD in 79.4% (95% CI, 77.1-81.6) for aortic stenosis, 77.6% (95% CI, 69.9-84.0) for aortic regurgitation, 68.5% (95% CI, 60.8-75.4) for mitral stenosis, and 71.0% (95% CI, 66.4-75.3) for primary mitral regurgitation. Valvular interventions were performed in 2150 patients during the survey; of them, 47.8% of patients with single left-sided native VHD were in New York Heart Association class III or IV. Transcatheter procedures were performed in 38.7% of patients with aortic stenosis and 16.7% of those with mitral regurgitation. CONCLUSIONS: Despite good concordance between Class I recommendations and practice in patients with aortic VHD, the suboptimal number in mitral VHD and late referral for valvular interventions suggest the need to improve further guideline implementation.

Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus.

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.

Correlation Between Echocardiographic and Hemodynamic Variables in Cardiothoracic Intensive Care Unit.

OBJECTIVES: The echocardiographic indices have not been validated in critically ill population. The authors investigated the correlation between some echocardiographic and hemodynamic parameters. DESIGN: Prospective, spontaneous, noninterventional observational study. SETTING: Adult cardiothoracic intensive care unit, single center (Royal Brompton Hospital, London, United Kingdom). PARTICIPANTS: Consecutive adult patients admitted to the cardiothoracic intensive care unit for severe respiratory failure, primary cardiocirculatory failure, and post-aortic surgery. INTERVENTIONS: Clinical hemodynamic parameters (stroke volume [SV], cardiac output [CO], mean arterial pressure [MAP], and cardiac power index [CPI]) and echocardiographic indices of ventricular function (left ventricular total isovolumic time [t-IVT], mitral annular plane systolic excursion [MAPSE], and left ventricular fraction [LVEF]) were evaluated offline. MEASUREMENTS AND MAIN RESULTS: The study comprised 117 patients (age 57.2 ± 19; 60.6% male). The t-IVT showed an inverse correlation with SV, CO, MAP, and CPI (r -67%; -38%; -45%; -51%, respectively). MAPSE exhibited a positive correlation with SV, CO, MAP, and CPI (r 43%; 44%; 34%; 31%, respectively). LVEF did not show any correlation. In the multivariate analysis the association between t-IVT and hemodynamics was confirmed for SV, CO, MAP, and CPI, with the highest partial correlation between t-IVT and MAP (R = -58%). CONCLUSIONS: MAPSE and t-IVT are 2 reproducible and reliable echocardiographic indices of systolic function and ventricular efficacy associated with hemodynamic variables in cardiothoracic critically ill patients, whereas LVEF did not show any correlation.

Right ventricular total isovolumic time: Reference value study.

BACKGROUND: There is lack of noninvasive indices to detail the right side cardiovascular physiology. Total isovolumic time (tIVT) is a sensitive marker of left ventricular electromechanical efficiency and systolic-diastolic interaction. The aim of the study was to evaluate normal reference value of the right ventricular tIVT with increasing age. METHODS AND RESULTS: One hundred and eighty-one healthy volunteers (51% male) underwent transthoracic echocardiography. The population was divided into four categories according to age: A < 30 years; B 30-39 years; C 40-49 years; and C ≥ 50 years old. tIVT was computed in seconds/minutes as: 60 - (tET + tFT). tET and tFT are the total ejection and filling time adjusted by the heart rate, measured, respectively, from the onset to the end of the right ventricle (RV) forward flow through the pulmonary valve and from the onset of the E-wave and the end of the A-wave at the level of the tricuspid valve. The mean RV tIVT was 7 ± 1.1 s/min and increased significantly with age, from a 3.4 to 9.7 s/min(P < 0.0001). Significant correlation was found between tIVT and trans-tricuspid E/E' (P < 0.0001; 0.78 (95% CI: 0.715-0.831) while weaker between tIVT and E/A (P = 0.001; -0.283 95% CI: -0.413 to -0.143). CONCLUSION: The normal values of RV tIVT increase with age and correlate significantly with Doppler diastolic parameters.