Long term impact of cardiac contractility modulation on QRS duration.

BACKGROUND AND PURPOSE: Cardiac contractility modulation (CCM) is an implantable device treatment for heart failure with reduced ejection fraction. CCM therapy improves patient functional status but its effect on intra-ventricular conduction remains unknown. METHODS: 70 patients treated with CCM between 12/2002 and 5/2013 had 12-vector-ECG recordings made at baseline and final follow-up visits. QRS complex duration was measured at each time point. RESULTS: Mean follow-up was 2.8 years. Mean QRS duration was unchanged from baseline (112.0 ms) to last follow up (112.9 ms, p=n.s.). These results are strikingly different from comparative published data of several studies with heart failure patients without CCM, consistently indicating an increase in QRS duration (6.0-23.4 ms) over a similar time period. CONCLUSIONS: CCM prevents chronic ventricular depolarization delay that occurs in heart failure and that is associated with poorer outcomes. This supports the safety of long-term CCM therapy and suggests a possible long-term benefit in maintaining QRS duration.

Global and regional myocardial function quantification in Takotsubo cardiomyopathy in comparison to acute anterior myocardial infarction using two-dimensional (2D) strain echocardiography.

AIMS: This study sought to compare global and regional myocardial function in Takotsubo cardiomyopathy (TC) to that in acute anterior myocardial infarction (AMI) using 2D strain imaging. METHODS: Twelve consecutive patients with TC (ten women, two men) and 12 patients with AMI (four women, eight men) underwent 2D echocardiography at initial presentation. 2D strain images were analyzed to measure longitudinal and radial strain. Global strain was calculated as the average longitudinal strain of the segments of two-, three-, and four-chamber views. Biplane ejection fraction was assessed using Simpson's biplane method. RESULTS: Significant differences in radial strain (TC vs. AMI) were found in lateral (13.5 ± 10.1% vs. 25.1 ± 11.2%, P = 0.035), posterior (15.2 ± 14.5% vs. 51.4 ± 14.2%, P < 0.001), and inferior (17.9 ± 15.5% vs. 49.4 ± 16.9%, P = 0.002) segments. Longitudinal strain was significantly lower in TC in basal-inferior (-15.8 ± 9.2% vs. -22.7 ± 3.8%, P = 0.037), midinferior (-8.3 ± 9.2% vs. -16.8 ± 3.0%, P = 0.004), basal-posterior (-12.2 ± 9.4% vs. -21.6 ± 4.4%, P = 0.016), midposterior (-4.4 ± 8.0% vs. -15.4 ± 3.5%, P = 0.002), apical-posterior (2.3 ± 6.7% vs. -6.4 ± 10.1%, P = 0.023), and midlateral (-3.4 ± 6.9% vs. -9.5 ± 5.8%, P = 0.028) segments. Global strain and ejection fraction were significantly higher in patients with AMI (-3.5 ± 8.2% vs. -10.3 ± 8.4%, P < 0.001 and 37 ± 11% vs. 46 ± 11%, P = 0.045). CONCLUSION: In TC, strain was reduced around the entire mid left-ventricular circumference, whereas in AMI it was predominantly reduced in the anterior and anteroseptal wall. These observed differences confirm the notion that TC affects myocardium beyond the territory of a single coronary artery. They may allow noninvasive distinction between both entities.

[Is cardiotoxicity still an issue after breast-conserving surgery and could it be reduced by multifield IMRT?]. / Ist die Kardiotoxizität der Radiotherapie im Rahmen des Brusterhalts überhaupt noch relevant, und könnte sie durch Mehrfelder-IMRT gesenkt werden?

BACKGROUND: Postoperative radiotherapy after breast cancer surgery effectively reduces local relapses. A survival benefit after breast conservation, however, has only been proven recently which was in part due to excessive cardiac mortality of patients who had been treated with radiotherapy in the past. MATERIAL AND METHODS: The literature on postoperative radiotherapy for breast cancer was reviewed with regard to cardiac toxicity as the basis for hypothesis generation. RESULTS: From numerous publications on cardiac toxicity of breast cancer radiotherapy, the following pattern emerges: in series where a high radiation dose was applied to a significant percentage of the heart (postmastectomy and postlumpectomy series) cardiac toxicity/mortality was increased versus a nonexposed cohort or for left over right disease. If, however, a relevant exposure of cardiac muscle could be more or less excluded based on the technique used (mainly more recent postlumpectomy radiotherapy), no cardiac toxicity was observed. Series for which individual dose exposure varied or could not be clarified also came to varying conclusions. Also due to retrospectively unclear dose distributions, an exact quantification of tolerance doses/effects of different geographic dose distribution patterns could not be performed to date. A particularly difficult question to answer is the threshold volume for clinically relevant cardiotoxicity with tangential radiotherapy at prescription doses. As a consequence, this precludes an estimate in which situations multifield intensity-modulated radiotherapy (IMRT) with its characteristic dose distribution pattern of a larger volume exposed to intermediate doses and higher mean/median heart doses (as shown in Figure 1) might be preferable. CONCLUSION: This review updates the database on cardiac toxicity of breast cancer radiotherapy with special emphasis regarding the issues related to the clinical use of IMRT. Multifield IMRT may reduce the cardiac risk for a small subset of patients at excessive risk with conventional tangential radiotherapy due to unfavorable thoracic geometry, for whom partial-breast radiotherapy is not an option. Due to further concern about the effects of intermediate doses to larger heart volumes, potentially increased contralateral cancer risk and the long latency of clinically apparent toxicity, the introduction of breast IMRT should be closely followed. Accompanying functional studies may have the potential to detect cardiac toxicity at an earlier time.

Global and regional myocardial function quantification by two-dimensional strain in Takotsubo cardiomyopathy.

AIMS: This study sought to characterize global and regional systolic function in Takotsubo cardiomyopathy (TC) using two-dimensional (2D) strain imaging. METHODS AND RESULTS: Twelve consecutive patients (11 women, 1 man) underwent 2D echocardiography on admission and on early follow-up (34 +/- 16 days). Two-dimensional images were analysed to measure longitudinal and radial strain and to calculate post-systolic shortening (PSS) and the post-systolic index (PSI). Mean age was 64 +/- 14 years. Upon presentation ejection fraction, average longitudinal and radial strains were 42 +/- 9%, -10.6 +/- 5.5%, and 20.1 +/- 17.3%, respectively. Values improved to 59 +/- 8%, -17.6 +/- 3.0%, and 50.2 +/- 17.0%, respectively (all P < 0.001). PSS was present in 69% of segments upon presentation and in 53% of segments upon follow-up. PSI was -0.16 at baseline and improved to -0.06 upon follow-up (P < 0.001). CONCLUSION: Patients with TC show abnormal global and regional strain patterns during the acute phase of the disease which improve over time. However, subtle abnormalities of regional LV function seem to persist into the early follow-up period as suggested by the presence of PSS in more than half of LV segments. Long-term follow-up studies are needed to clarify whether these subtle abnormalities will further improve.

Clinical and echocardiographic analysis of patients suffering from recurrent takotsubo cardiomyopathy.

BACKGROUND: Recurrence of takotsubo cardiomyopathy (TTC) is a well-known complication. However, current literature lists only a few isolated cases. We aimed to determine the incidence and clinical significance of recurrent TTC. METHODS & RESULTS: Our institutional database constituted a collective of 114 patients diagnosed with TTC since 2003. Close follow-up of these patients revealed a recurrence of TTC in seven of these (6.1%). The time interval between the index event and its recurrence varied between six months and six years. Arterial hypertension was more revealed in the recurrence group of TTC compared to non-recurrence group, (P = 0.02). Chronic obstructive pulmonary disease and/or asthma was more diagnosed in the recurrence group, (P = 0.04). Clinical events like right ventricular involvement, TTC related complications such as life-threatening arrhythmias, pulmonary congestion and in hospital death were observed more frequently in the recurrent episode. Over a mean follow-up of one year the mortality rate was similar in both groups. CONCLUSIONS: Recurrence of TTC within six years after index event is not an uncommon phenomenon. In the event of right ventricular involvement in the relapse phase, it might be associated with a higher complication rate. TTC recurrence should be the first differential diagnosis in patients with a past history of TTC.

Prevalence, Clinical Characteristics, and Predictors of Patients with Thromboembolic Events in Takotsubo Cardiomyopathy.

BACKGROUND: Several acute complications related to takotsubo cardiomyopathy (TTC) have been documented recently. However, the incidence and clinical significance of acute thromboembolic events in TTC is not well established. METHODS: A detailed investigation of the clinical characteristics and in-hospital complications of 114 consecutive patients diagnosed with TTC between January 2003 and September 2015 was carried out. This study was initiated to reveal the predictors, clinical significance, and short-term and long-term outcomes of patients with TTC associated with acute thromboembolic events on index presentation. RESULTS: The incidence of acute thromboembolic events related to TTC was around 12.2%, and these included ventricular thrombi, cerebrovascular events, retinal and brachial artery pathologies, renal, splenic, and aortic involvement. The most frequent complication on initial presentation was cardiogenic shock (20%) accompanied with pulmonary congestion (20%). Interestingly, patients experiencing thromboembolic events had higher C-reactive protein (CRP) levels as compared to the non-thromboembolic group (P = 0.02). Certain thromboembolic events were characterized by the presence of ST-segment elevation in electrocardiogram (P = 0.02). Chest pain was the primary symptom in these patients (P = 0.09). Furthermore, there was significant right ventricular involvement (as assessed by transthoracic echocardiography) in patients presenting with an acute thromboembolic event (P = 0.08). A Kaplan-Meier analysis indicated a significantly higher mortality rate over a mean follow-up of three years in the thromboembolic group than the non-thromboembolic group (log-rank, P = 0.02). CONCLUSIONS: Our results confirmed the relative common occurrence of thromboembolic events in the setting of TTC. Inflammation might play an important role in the development of thromboembolic events, and a right ventricular involvement and ST-segment elevation could be positive predictors for this occurrence. In order to circumvent the risk of a negative outcome, it is recommended that an anticoagulation therapy be initiated in all high-risk patients.

Cardiac Function After Multimodal Breast Cancer Therapy Assessed With Functional Magnetic Resonance Imaging and Echocardiography Imaging.

PURPOSE: Breast intensity modulated radiation therapy (IMRT) reduces high-dose heart volumes but increases low-dose volumes. We prospectively assessed heart changes after 3D conformal RT (3DCRT) and IMRT for left-sided breast cancer. Heart dose was analyzed individually, 3DCRT patients were moderately exposed, and IMRT was performed only in patients with unacceptably high heart doses upon 3DCRT planning. METHODS AND MATERIALS: In 49 patients (38 patients received 3DCRT; 11 patients received IMRT; and 20 patients received neoadjuvant or adjuvant chemotherapy) magnetic resonance imaging (MRI) and echocardiography were performed before and at 6, 12, and 24 months after treatment. RESULTS: Mean heart dose for IMRT was 12.9 ± 3.9 Gy versus 4.5 ± 2.4 Gy for 3DCRT. Heart volumes receiving >40 Gy were 2.6% (3DCRT) versus 1.3% (IMRT); doses were >50 Gy only with 3DCRT. Temporary ejection fraction (EF) decrease was observed on MRI after 6 months (63%-59%, P=.005) resolving at 24 months. Only 3 patients had pronounced largely transient changes of EF and left ventricular enddiastolic diameter (LVEDD). Mitral (M) and tricuspid (T) annular plane systolic excursion (MAPSE and TAPSE) were reduced over the whole cohort (still within normal range). After 24 months left ventricular remodeling index decreased in patients receiving chemotherapy (0.80 vs 0.70, P=.028). Neither wall motion abnormalities nor late enhancements were found. On echocardiography, in addition to EF findings that were similar to those on MRI, global strain was unchanged over the whole cohort at 24 months after a transient decrease at 6 and 12 months. Longitudinal strain decreased in the whole cohort after 24 months in some segments, whereas it increased in others. CONCLUSIONS: Until 24 months after risk-adapted modern multimodal adjuvant therapy, only subclinical cardiac changes were observed in both 3DCRT patients with inclusion of small to moderate amounts of heart volume in RT tangents and in the patients treated with IMRT and reduced high-dose heart exposure.

Mitral annular plane systolic excursion is an easy tool for fibrosis detection by late gadolinium enhancement cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) causes various degrees of fibrosis resulting in left ventricular function impairment, which can be measured using mitral annular plane systolic excursion (MAPSE). AIMS: To determine the values for septal, lateral and average MAPSE using cardiovascular magnetic resonance (CMR) in healthy controls and patients with HCM; and to investigate whether MAPSE correlated with the extent of fibrosis. METHODS: Patients with HCM and healthy controls underwent CMR. RESULTS: In 50 healthy controls, septal and lateral MAPSE were comparable and showed excellent intra- and inter-observer reliability. Patients with HCM had significantly reduced septal, lateral and average MAPSE compared to healthy controls. Furthermore, in patients with HCM, septal MAPSE measurements were significantly reduced compared to lateral ones. Correspondingly, the septal myocardial segments showed significantly more late gadolinium enhancement (LGE) than lateral ones. No significant differences were found between echocardiographic and CMR MAPSE measurements in healthy controls and patients with HCM. Patients who suffered a major adverse cardiac event or stroke revealed a significantly reduced MAPSE and a significantly greater LGE extent compared to event-free patients with HCM. CONCLUSIONS: MAPSE measurement using CMR is feasible, reproducible and comparable to echocardiography in healthy controls and patients with HCM. The asymmetric and mainly septal distribution of myocardial hypertrophy and fibrosis detected by LGE in patients with HCM was reflected by significantly reduced septal versus lateral MAPSE. Therefore, reduced MAPSE seems to be an easily determinable marker of fibrosis accumulation leading to left ventricular mechanical dysfunction and also seems to have a prognostic implication.

Right ventricular function quantification in Takotsubo cardiomyopathy using two-dimensional strain echocardiography.

AIMS: This study sought to characterize global and regional right ventricular (RV) myocardial function in patients with Takotsubo cardiomyopathy (TC) using 2D strain imaging. METHODS: We compared various parameters of RV and left ventricular (LV) systolic function between 2 groups of consecutive patients with TC at initial presentation and upon follow-up. Group 1 had RV involvement and group 2 did not have RV involvement. RESULTS: At initial presentation, RV peak systolic longitudinal strain (RVPSS) and RV fractional area change (RVFAC) were significantly lower in group 1 (-13.2±8.6% vs. -21.8±5.4%, p = 0.001; 30.7±9.3% vs. 43.5±6.3%, p = 0.001) and improved significantly upon follow-up. Tricuspid annular plane systolic excursion (TAPSE) did not differ significantly at initial presentation between both groups (14.8±4.1 mm vs. 17.9±3.5 mm, p = 0.050). Differences in regional systolic RV strain were only observed in the mid and apical segments. LV ejection fraction (LVEF) and LV global strain were significantly lower in group 1 (36±8% vs. 46±10%, p = 0.006 and -5.5±4.8% vs. -10.2±6.2%, p = 0.040) at initial presentation. None of the parameters were significantly different between the 2 groups upon follow-up. A RVPSS cut-off value of >-19.1% had a sensitivity of 85% and a specificity of 71% to discriminate between the 2 groups. CONCLUSION: In TC, RVFAC, RVPSS, LVEF and LV global strain differed significantly between patients with and without RV dysfunction, whereas TAPSE did not. 2 D strain imaging was feasible for the assessment of RV dysfunction in TC and could discriminate between patients with and without RV involvement in a clinically meaningful way.

Epicardial adipose tissue assessed by cardiac magnetic resonance imaging in patients with heart failure due to dilated cardiomyopathy.

OBJECTIVE: We sought to investigate the association of the EAT with CMR parameters of ventricular remodelling and left ventricular (LV) dysfunction in patients with non-ischemic dilated cardiomyopathy (DCM). DESIGN AND METHODS: One hundred and fifty subjects (112 consecutive patients with DCM and 48 healthy controls) underwent CMR examination. Function, volumes, dimensions, the LV remodelling index (LVRI), the presence of late gadolinium enhancement (LGE) and the amount of EAT were assessed. RESULTS: Compared to healthy controls, patients with DCM revealed a significantly reduced indexed EAT mass (31.7 ± 5.6 g/m(2) vs 24.0 ± 7.5 g/m(2) , p<0.0001). There was no difference in the EAT mass between DCM patients with moderate and severe LV dysfunction (23.5 ± 9.8 g/m(2) vs 24.2 ± 6.6 g/m(2) , P = 0.7). Linear regression analysis in DCM patients showed that with increasing LV end-diastolic mass index (LV-EDMI) (r = 0.417, P < 0.0001), increasing LV end-diastolic volume index (r = 0.251, P = 0.01) and increasing LV end-diastolic diameter (r = 0.220, P = 0.02), there was also a significantly increased amount of EAT mass. However, there was no correlation between the EAT and the LV ejection fraction (r = 0.0085, P = 0.37), right ventricular ejection fraction (r = 0.049, P = 0.6), LVRI (r = 0.116, P = 0.2) and the extent of LGE % (r = 0.189, P = 0.1). Among the healthy controls, the amount of EAT only correlated with increasing age (r = 0.461, P = 0.001), BMI (r = 0.426, P = 0.003) and LV-EDMI (r = 0.346, P = 0.02). CONCLUSION: In patients with DCM the amount of EAT is decreased compared to healthy controls irrespective of LV function impairment. However, an increase in LV mass and volumes is associated with a significantly increase in EAT in patients with DCM.

Evaluation of aortic valve stenosis using a hybrid approach of Doppler echocardiography and inert gas rebreathing.

BACKGROUND: Doppler echocardiography is the method of choice for diagnosis and evaluation of aortic stenosis. However, there are well-known limitations to this method in difficult-to-image patients. Flow acceleration in the left ventricular outflow tract (LVOT) can lead to overestimation of stroke volume (SV) and poor acoustic windows may impede the exact measurement of the LVOT. The present study aimed to evaluate the use of inert gas rebreathing (IGR)-derived SV in this situation. PATIENTS AND METHODS: We replaced Doppler-derived SV measurements in the continuity equation (method A) by SV determined by IGR (method B) and by thermodilution during right heart catheterization (method C) to calculate the aortic valve area (AVA) in 21 consecutive patients with moderate or severe aortic stenosis. RESULTS: Mean SV and AVA did not differ between methods at 72±21 ml and 0.71±0.2 cm(2) (method A) vs. 66±18 ml and 0.67±0.21 cm(2) (method B) vs. 64±15 ml and 0.67±0.21 cm(2) (method C), respectively (all p-values >0.05). The mean difference and limits of agreement for AVA were 0.04±0.23 cm(2) and -0.40 to 0.47 cm(2) between methods A and B, 0.05±0.14 cm(2) and -0.26 to 0.27 cm(2) between A and C, and -0.05±0.23 cm(2) and -0.45 to 0.35 cm(2) between B and C, respectively (all p-values >0.05). CONCLUSION: The presented approach is a reliable method for the calculation of AVA and can add a diagnostic option for the use in difficult-to-image patients. Whereas the use of thermodilution is limited due to its invasive nature, IGR allows the fast and non-invasive determination of cardiac function at low cost.