Heart rate and dyssynchrony in patients with cardiac resynchronization therapy: a pilot study.

OBJECTIVES: The objective of this pilot study was to describe the impact of paced heart rate on left ventricular (LV) mechanical dyssynchrony in synchronous compared to dyssynchronous pacing modes in patients with heart failure. METHODS: Echocardiography was performed in 14 cardiac resynchronization therapy (CRT) patients at paced heart rates of 70 and 90 bpm in synchronous- (CRT), and dyssynchronous (atrial pacing + wide QRS activation) pacing modes. LV dyssynchrony was quantified using the 12-segment standard deviation model (Ts-SD) derived from Tissue Doppler Imaging. In addition, cardiac cycle intervals were assessed using cardiac state diagrams and stroke volume (SV) and filling pressure were estimated. RESULTS: Ts-SD decreased significantly with CRT at 90 bpm (25 ± 12 ms) compared to 70 bpm (35 ± 15 ms, p = .01), but remained unchanged with atrial pacing at different paced heart rates (p = .96). The paced heart rate dependent reduction in Ts-SD was consistent when Ts-SD was indexed to average Ts and systolic time interval. Cardiac state diagram derived analysis of cardiac cycle intervals demonstrated a significant reduction of the pre-ejection interval and an increase in diastole with CRT compared to atrial pacing. SV was maintained at the higher paced heart rate with CRT pacing but decreased with atrial pacing. DISCUSSION: Due to the small sample size in this pilot study general and firm conclusions are difficult to render. However, the data suggest that pacing at higher heart rates acutely reduces remaining LV dyssynchrony during CRT, but not during atrial pacing with dyssynchronous ventricular activation. These results need confirmation in a larger patient cohort.

The potential clinical value of contrast-enhanced echocardiography beyond current recommendations.

BACKGROUND: Contrast agents are used in resting echocardiography to opacify the left ventricular (LV) cavity and to improve LV endocardial border delineation in patients with suboptimal image quality. If a wider use of contrast-enhanced echocardiography would be adopted instead of the current selective approach, diagnoses such as myocardial ischemia and LV structural abnormalities could potentially be detected earlier. The aim was therefore to retrospectively investigate if contrast-enhanced echocardiography beyond the current recommendations for contrast agent usage affects assessment of wall motion abnormalities, ejection fraction (EF) and detection of LV structural abnormalities. A secondary aim was to evaluate the user dependency during image analysis. METHODS: Experienced readers (n = 4) evaluated wall motion score index (WMSI) and measured EF on greyscale and contrast-enhanced images from 192 patients without indications for contrast-enhanced echocardiography. Additionally, screening for LV structural abnormalities was performed. Repeated measurements were performed in 20 patients by the experienced as well as by inexperienced (n = 2) readers. RESULTS: Contrast analysis resulted in significantly higher WMSI compared to greyscale analysis (p < 0.003). Of the 83 patients, classified as healthy by greyscale analysis, 55% were re-classified with motion abnormalities by contrast analysis. No significant difference in EF classification (≥55%, 45-54%, 30-44%, < 30%) was observed. LV structural abnormalities, such as increased trabeculation (n = 21), apical aneurysm (n = 4), hypertrophy (n = 1) and thrombus (n = 1) were detected during contrast analysis. Intra- and interobserver variability for experienced readers as well as the variability between inexperienced and experienced readers decreased for WMSI and EF after contrast analysis. CONCLUSIONS: Contrast-enhanced echocardiography beyond current recommendations for contrast agent usage increased the number of detected wall motion and LV structural abnormalities. Moreover, contrast-enhanced echocardiography increased reproducibility for assessment of WMSI and EF.

Effects of neoadjuvant chemo or chemoradiotherapy for oesophageal cancer on perioperative haemodynamics: A prospective cohort study within a randomised clinical trial.

BACKGROUND: Neoadjuvant chemoradiotherapy might improve oncological outcome compared with chemotherapy after surgery for oesophagus or gastrooesophageal junction cancer. However, radiotherapy may induce cardiovascular side-effects that could increase the risk of perioperative adverse effects and postoperative morbidity. OBJECTIVES: The aim of this study was to compare the perioperative haemodynamics in patients undergoing oesophagectomy following neoadjuvant chemotherapy or chemoradiotherapy for cancer. DESIGN: A prospective single-centre cohort study within a randomised multi-centre trial. SETTING: A Swedish University Hospital from January 2009 to March 2013. PATIENTS: A total of 31 patients (chemotherapy 17, chemoradiotherapy 14) included in a multi-centre trial randomising chemotherapy vs. chemoradiotherapy and operated at Karolinska University Hospital, Huddinge. INTERVENTIONS: Cisplatin and 5-fluorouracil, either with or without concurrent radiotherapy (40 Gy), were given prior to surgery. Cardiac function was assessed with LiDCOplus (LiDCO Ltd, London, United Kingdom), echocardiography, troponin T and N-terminal pro-B-type natriuretic peptide, before, during and after surgery. MAIN OUTCOME MEASURES: The primary outcome was the interaction effect of the neoadjuvant treatment on stroke volume index during the perioperative period. Secondary outcomes were the interaction effects of oxygen delivery index, cardiac index, echocardiography and biochemical markers. RESULTS: The groups were matched regarding comorbidities, but patients in the chemoradiotherapy group were older (66 vs. 60 years P = 0.03). Haemodynamic values changed in a similar way in both groups during the study period. The chemoradiotherapy group had a lower cardiac index before surgery (2.9 vs. 3.4 l min m, P = 0.03). On the third postoperative day, both groups displayed a hyperdynamic state compared with baseline, with no increase in troponin T, and a similar increase in N-terminal pro-B-type natriuretic peptide. CONCLUSION: Neoadjuvant chemoradiotherapy for oesophageal or gastrooesophageal junction cancer seems to induce only a marginal negative effect on cardiac function compared with neoadjuvant chemotherapy. This difference did not remain when patients' haemodynamics were challenged by surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01362127.

The impact of arterial load on left ventricular performance: an invasive haemodynamic study in severe mitral stenosis.

KEY POINTS: A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading. As most of the methods used to determine LV performance in MS patients are influenced by loading conditions, previous studies have shown conflicting results. The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways. Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness. Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS. ABSTRACT: Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load-independent indices robust to the altered loading state. We studied 106 subjects (32 ± 8 years, 72% female) with severe MS (0.8 ± 0.2 cm(2) ) and 40 age-matched controls. MS subjects underwent simultaneous bi-ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single-beat LV elastance (Ees ) was employed for LV contractility measurements. Effective arterial elastance (Ea ) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea : 3.0 ± 1.3 vs. 1.5 ± 0.3 mmHg ml(-1) ; P < 0.001) and LV contractility (Ees : 4.1 ± 1.6 vs. 2.4 ± 0.5 mmHg ml(-1) ; P < 0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8 cm(2) ) and pronounced subvalvular fusion. Stroke volume (49 ± 16 to 57 ± 17 ml; P < 0.001) and indexed LV end-diastolic volume (LVEDVindex : 57 ± 16 to 64 ± 16 ml m(-2) ; P < 0.001) increased following PTMC while Ees and Ea returned to more normal levels. Elevated LV stiffness was demonstrated at baseline and increased further following PTMC. Our findings provide evidence of elevated LV contractility, increased arterial load and increased diastolic stiffness in severe MS. Following PTMC, both LV contractility and afterload tend to normalize.

The pulmonary capillary wedge pressure accurately reflects both normal and elevated left atrial pressure.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) is routinely used as an indirect measure of the left atrial pressure (LAP), although the accuracy of this estimate, especially under pathological hemodynamic conditions, remains controversial. OBJECTIVES: The aim of this prospective study was to investigate the reliability of PCWP for the evaluation of LAP under different hemodynamic conditions. METHODS: Simultaneous left and right heart catheterization data of 117 patients with pure mitral stenosis, obtained before and immediately after percutaneous mitral comissurotomy, were analyzed. RESULTS: A strong correlation and agreement between PCWP and LAP measurements was demonstrated (correlation coefficient = 0.97, mean bias ± CI, 0.3 ± -3.7 to 4.2 mm Hg). Comparison of measurements performed within a 5-minute interval and those performed simultaneously revealed that simultaneous pressure acquisition yielded better agreement between the 2 methods (bias ± CI, 1.82 ± 1.98 mm Hg). In contrast to previous observations, the discrepancy between the 2 measures did not increase with elevated PCWP. Multiple regression analysis failed to identify hemodynamic confounders of the discrepancy between the 2 pressures. The ability of PCWP to distinguish between normal and elevated LAP (cutoff set at 12 and 15 mm Hg, respectively), as tested by receiver operating characteristics analysis, demonstrated a remarkably high diagnostic accuracy (area under the curve: 0.989 and 0.996, respectively). CONCLUSIONS: Although the described limits of agreement may not allow the interchangeability of PCWP and LAP, especially at lower pressure ranges, our data support the clinical use of PCWP as a robust and accurate estimate of LAP.

The prognostic value of mechanical left ventricular dyssynchrony in patients with acute coronary syndrome.

BACKGROUND: Echocardiography is a well-established tool for risk stratification in patients with acute coronary syndrome (ACS). ACS has significant impact on LV dyssynchrony, and detrimental effects on systolic function and long term outcome. The aims of this study were to determine whether LV dyssynchrony carries any predictive information in an unselected ACS population and to evaluate if it has any incremental value to the information given from conventional echocardiographic measurements. METHODS: The study included 227 consecutive ACS patients. Primary endpoint was the composite of death, new MI, or rehospitalisation due to heart failure. Dyssynchrony was measured as intersegmental variation of time to peak strain, the post systolic index (PSI) and myocardial performance index (MPI) with the standard deviation and difference between lowest and highest value (delta) expressing the amount of dyssynchrony. Septal-lateral delay was also tested. All dyssynchrony parameters were compared with Ejection fraction (EF). RESULTS: The median follow up time was 53 months. 85 patients reached the combined endpoint. Patients with and without a subsequent combined endpoint differed significantly regarding calculated SD: s and delta-value for PSI, time to peak 2D-strain and MPI but not regarding septal-lateral delay. In ROC-analysis none of the dyssynchrony parameters had larger AUC than EF. When adjusting for traditional risk factors none of the dyssynchrony parameters remained associated with outcome, whereas EF still did. CONCLUSION: LV dyssynchrony seem to have significant prognostic information in patient with acute coronary syndrome but in comparison to conventional parameters such as EF there is no incremental value of this information.

Peak systolic velocity using color-coded tissue Doppler imaging, a strong and independent predictor of outcome in acute coronary syndrome patients.

BACKGROUND: Traditional echocardiographic methods like left ventricular ejection fraction(EF) and wall motion scoring (WMS) and new methods like speckle tracking (ST) based 2D strain carry important prognostic information in acute coronary syndrome (ACS) patients. Parameters from tissue Doppler imaging (TDI), with its high time resolution, may further increase the prognostic value. Peak systolic velocity (PSV) of the basal segments of the left ventricle from TDI is a robust and user independent parameter. The aim was to investigate the prognostic value of PSV compared to EF, WMS, 2D strain and E/e'. METHODS: Echocardiographic images were collected and post processed in 227 ACS patients. Additional clinical data was prospectively gathered and patients were followed for 3-5 years regarding the combined endpoint of death or re-admission due to ACS or heart failure. RESULTS: The combined endpoint occurred in 85 (37%) patients. Those with an event had lower median PSV than those without (4,4 cm/s) vs. (5,3 cm/s), (p<0.001). In a ROC analysis, the AUC was larger for PSV (0.75) than for EF (0.68), WMS (0.63), 2D strain (0.67) and E/e'(0.70). The combined endpoint increased with decreasing PSV. When adjusting for differences in baseline characteristics in a COX-regression model, PSV remained independently associated with outcome where the others did not. PSV was also less sensitive to image quality with fewer values missing or unacceptable for analysis. CONCLUSION: Peak systolic velocity (PSV) is a robust measurement that seems to have a strong and independent association with outcome compared to traditional echocardiographic measurements in ACS patients.

Altered ventriculo-arterial coupling during exercise in athletes releasing biomarkers after endurance running.

Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood phenomenon proposed to especially occur with high-intensity exercise in less trained subjects. We hypothesised that haemodynamic perturbations during exercise are larger in athletes with cTnT release, and studied athletes with detectable cTnT levels after an endurance event (HIGH; n = 16; 46 ± 9 years) against matched controls whose levels were undetectable (LOW; n = 11; 44 ± 7 years). Echocardiography was performed at rest and at peak supine bicycle exercise stress. Left ventricular (LV) end-systolic elastance (E (LV) a load-independent measure of LV contractility), effective arterial elastance (E (A) a lumped index of arterial load) and end-systolic meridional wall stress were calculated from cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was judged from the ventriculo-arterial coupling ratio (E (A)/E (LV): optimal range 0.5-1.0). While subgroups had similar values at rest, we found ventriculo-arterial mismatch during exercise in HIGH subjects [0.47 (0.39-0.58) vs. LOW: 0.73 (0.62-0.83); p < 0.01] due to unopposed increase in E (LV) (p < 0.05). In LOW subjects, a greater increase occurred in E (A) during exercise (+81 ± 67 % vs. HIGH: +39 ± 32 %; p = 0.02) which contributed to a maintained coupling ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress during exercise (R (2) = 0.39; p < 0.01) despite no correlation at rest (p = ns). In conclusion, athletes with exercise-induced biomarker release exhibit ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work may contribute to this phenomenon.

Altered Aortic Hemodynamics and Relative Pressure in Patients with Dilated Cardiomyopathy.

Ventricular-vascular interaction is central in the adaptation to cardiovascular disease. However, cardiomyopathy patients are predominantly monitored using cardiac biomarkers. The aim of this study is therefore to explore aortic function in dilated cardiomyopathy (DCM). Fourteen idiopathic DCM patients and 16 controls underwent cardiac magnetic resonance imaging, with aortic relative pressure derived using physics-based image processing and a virtual cohort utilized to assess the impact of cardiovascular properties on aortic behaviour. Subjects with reduced left ventricular systolic function had significantly reduced aortic relative pressure, increased aortic stiffness, and significantly delayed time-to-pressure peak duration. From the virtual cohort, aortic stiffness and aortic volumetric size were identified as key determinants of aortic relative pressure. As such, this study shows how advanced flow imaging and aortic hemodynamic evaluation could provide novel insights into the manifestation of DCM, with signs of both altered aortic structure and function derived in DCM using our proposed imaging protocol.

Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients.

Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 ± 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve ≥15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients.