Notch ratio in pulmonary flow predicts long-term survival after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

BACKGROUND: Assessment of the pattern of the RV outflow tract Doppler provides insights into the hemodynamics of chronic thromboembolic pulmonary hypertension (CTEPH). We studied whether pre-operative assessment of timing of the pulmonary flow systolic notch by Doppler echocardiography is associated with long-term survival after pulmonary endarterectomy (PEA) for CTEPH. METHODS: Fifty-nine out of 61 consecutive CETPH patients (mean age 53 ± 14 years, 34% male) whom underwent PEA between June 2002 and June 2005 were studied. Clinical, echocardiographic and hemodynamic variables were assessed pre-operatively and repeat echocardiography was performed 3 months after PEA. Notch ratio (NR) was assessed with pulsed Doppler and calculated as the time from onset of pulmonary flow until notch divided by the time from notch until end of pulmonary flow. Long-term follow-up was obtained between May 2021 and February 2022. RESULTS: Pre-operative mean pulmonary artery pressure (mPAP) was 45 ± 15 mmHg and pulmonary vascular resistance (PVR) was 646 ± 454 dynes.s.cm-5. Echocardiography before PEA showed that 7 patients had no notch, 33 had a NR < 1.0 and 19 had a NR > 1.0. Three months after PEA, echocardiography revealed a significant decrease in sPAP in long-term survivors with a NR < 1.0 and a NR > 1.0, while a significant increase in TAPSE/sPAP was only observed in the NR < 1.0 group. Mean long-term clinical follow-up was 14 ± 6 years. NR was significantly different between survivors and non-survivors (0.73 ± 0.25 vs. 1.1 ± 0.44, p < 0.001) but no significant differences were observed in mPAP or PVR. Long-term survival at 14 years was significantly better in patients with a NR < 1.0 compared to patients with a NR > 1.0 (83% vs. 37%, p = < 0.001). CONCLUSION: Pre-operative assessment of NR is a predictor of long-term survival in CTEPH patients undergoing PEA, with low mortality risk in patients with NR < 1.0. Long-term survivors with a NR < 1.0 and NR > 1.0 had a significant decrease in sPAP after PEA. However, the TAPSE/sPAP only significantly increased in the NR < 1.0 group. In the NR < 1.0 group, the 6-min walk test increased significantly between pre-operative and at 1-year post-operative follow-up. NR is a simple echocardiographic parameter that can be used in clinical decision-making for PEA.

Worsening tricuspid regurgitation after ICD implantation is rather due to transvenous lead than natural progression.

BACKGROUND: Transvenous implantable cardioverter-defibrillators (TV-ICDs) are associated with greater tricuspid regurgitation (TR) severity, which leads to increased mortality. The pathophysiology is assumed to be lead-related, hence, treatment includes lead extraction. However, TR may also naturally occur in the high-risk ICD population, or may be caused by right ventricular pacing. We sought to evaluate the effect of ICD type (with or without lead) and pacing percentage on post-implantation TR severity. METHODS: In this retrospective cohort study, consecutive patients were included with a primary S-ICD or TV-ICD implantation between 2009 and 2019 and echocardiography studies ≤3 months before and ≤ 3 years post-implantation. The effect of ICD type on TR severity at follow-up was estimated adjusting for ventricular pacing percentage and potential confounders. The effect of ventricular pacing percentage on TR severity at follow-up was adjusted for potential confounders. RESULTS: 118 patients were included (mean age 52 ± 21): 31 (26%) with an S-ICD and 87 (74%) with a TV-ICD. Median 20 months post-implantation, worsening TR was found in 11/31 (34%) S-ICD patients and 45/87 (52%) TV-ICD patients (p = 0.15). Adjusted for age, atrial fibrillation, baseline TR and mitral regurgitation, ventricular pacing percentage, ICD dwelling time, BMI, hypertension and left ventricular ejection fraction, TV-ICDs were significantly associated with greater TR severity (OR 9.90, p = 0.002). Ventricular pacing percentage was very low, and not significantly associated with greater TR severity (OR 0.95, p = 0.066). CONCLUSIONS: Our results suggest that greater TR severity in ICD patients is mainly caused by the transvenous lead, rather than natural progression in the ICD population.

Can stress echocardiography identify patients who will benefit from percutaneous mitral valve repair?

The aim of the current study was to investigate whether stress echocardiography improves selection of patients who might have clinical benefit from percutaneous mitral valve repair with the MitraClip. In total, 39 patients selected for MitraClip implantation underwent preprocedural low-dose stress (dobutamine or handgrip) echocardiography from which stroke volume, ejection fraction and MR grade were measured. Outcome after MitraClip implantation was determined by New York Heart Association classification and Quality of Life questionnaires. Clinical benefit from MitraClip treatment was defined as survival and NYHA class I-II at 6 months follow-up. In total, 36 patients with a technically successful procedure were included in the analysis (mean age 79 ± 8 years, 47% male, 50% functional MR). Clinical benefit was achieved in 18 patients. All seven patients with MR decreasing during stress remained in NYHA III-IV or died within 6 months, while 62% (18 out of 29) of the patients with stable or increased MR during stress had clinical benefit (p = 0.008). Significant increase in Quality of Life on 4/8 subscales of the RAND Short Form-36 questionnaire was observed: Physical Functioning (p < 0.001), Social Functioning (p < 0.001), Mental Health (p = 0.022) and Vitality (p = 0.026) was seen in patients with an increase in stroke volume during stress echocardiography. Patients with a decreased MR during preprocedural stress echocardiography remained more symptomatic than patients with a stable or increased MR during stress. Stress echocardiography may support patient selection for percutaneous mitral valve repair.

Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer.

BACKGROUND AND PURPOSE: Neoadjuvant chemoradiation (nCRT) followed by surgery is considered curative intent treatment for patients with resectable esophageal cancer. The aim was to establish hemodynamic aspects of changes in heart volume and to explore whether changes in heart volume resulted in clinically relevant changes in the dose distribution of radiotherapy. METHODS: A prospective study was conducted in patients who were treated with nCRT consisting of carboplatin and paclitaxel concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction). Physical parameters, cardiac volume on CT and Cone beam CT, cardiac blood markers and cardiac ultrasound were obtained. RESULTS: In 23 patients a significant decrease of 55.3 ml in heart volume was detected (95% CI 36.7-73.8 ml, p<0.001). There was a decrease in both systolic (mean decrease 18 mmHg, 95% CI 11-26 mmHg, p<0.001) and diastolic blood pressure (mean decrease 8 mmHg, 95% CI 2-14 mmHg, p=0.008) and an increase in heart rate with 6 beats/min (95% CI 1-11 beats/min, p=0.021). Except for Troponin T, no change in other cardiac markers and echocardiography parameters were observed. The change in heart volume did not result in a clinically relevant change in radiation dose distribution. CONCLUSION: Heart volume was significantly reduced, but was not accompanied by overt cardiac dysfunction. All observed changes in hemodynamic parameters are consistent with volume depletion. Adaptation of the treatment plan during the course of radiotherapy is not advocated.

Electrophysiologic remodeling of the left ventricle in pressure overload-induced right ventricular failure.

OBJECTIVES: The purpose of this study was to analyze the electrophysiologic remodeling of the atrophic left ventricle (LV) in right ventricular (RV) failure (RVF) after RV pressure overload. BACKGROUND: The LV in pressure-induced RVF develops dysfunction, reduction in mass, and altered gene expression, due to atrophic remodeling. LV atrophy is associated with electrophysiologic remodeling. METHODS: We conducted epicardial mapping in Langendorff-perfused hearts, patch-clamp studies, gene expression studies, and protein level studies of the LV in rats with pressure-induced RVF (monocrotaline [MCT] injection, n = 25; controls with saline injection, n = 18). We also performed epicardial mapping of the LV in patients with RVF after chronic thromboembolic pulmonary hypertension (CTEPH) (RVF, n = 10; no RVF, n = 16). RESULTS: The LV of rats with MCT-induced RVF exhibited electrophysiologic remodeling: longer action potentials (APs) at 90% repolarization and effective refractory periods (ERPs) (60 ± 1 ms vs. 44 ± 1 ms; p < 0.001), and slower longitudinal conduction velocity (62 ± 2 cm/s vs. 70 ± 1 cm/s; p = 0.003). AP/ERP prolongation agreed with reduced Kcnip2 expression, which encodes the repolarizing potassium channel subunit KChIP2 (0.07 ± 0.01 vs. 0.11 ± 0.02; p < 0.05). Conduction slowing was not explained by impaired impulse formation, as AP maximum upstroke velocity, whole-cell sodium current magnitude/properties, and mRNA levels of Scn5a were unaltered. Instead, impulse transmission in RVF was hampered by reduction in cell length (111.6 ± 0.7 µm vs. 122.0 ± 0.4 µm; p = 0.02) and width (21.9 ± 0.2 µm vs. 25.3 ± 0.3 µm; p = 0.002), and impaired cell-to-cell impulse transmission (24% reduction in Connexin-43 levels). The LV of patients with CTEPH with RVF also exhibited ERP prolongation (306 ± 8 ms vs. 268 ± 5 ms; p = 0.001) and conduction slowing (53 ± 3 cm/s vs. 64 ± 3 cm/s; p = 0.005). CONCLUSIONS: Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV.

Adults with Down syndrome have reduced cardiac response after light exercise testing.

OBJECTIVE: Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS. DESIGN: Case controlled before-after trial. SETTING: Residential centre for people with intellectual disabilities. PARTICIPANTS: 96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls. INTERVENTIONS: Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends. MAIN OUTCOME MEASURE: Exercise testing RESULTS: At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m(2), p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m(2), p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response. CONCLUSIONS: CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent.

Right ventricular pacing improves haemodynamics in right ventricular failure from pressure overload: an open observational proof-of-principle study in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Right ventricular (RV) failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH), and other types of pulmonary arterial hypertension is associated with right-to-left ventricle (LV) delay in peak myocardial shortening and, consequently, the onset of diastolic relaxation. We aimed to establish whether RV pacing may resynchronize the onsets of RV and LV diastolic relaxation, and improve haemodynamics. METHODS AND RESULTS: Fourteen CTEPH patients (mean age 63.7 ± 12.0 years, 10 women) with large (≥60 ms) RV-to-LV delay in the onset of diastolic relaxation (DIVD, diastolic interventricular delay) were studied. Temporary RV pacing was performed by atrioventricular (A-V) sequential pacing with incremental shortening of A-V delay to advance RV activation. Effects were assessed using tissue Doppler echocardiography and LV pressure-conductance catheter measurements in a subset of patients. Compared with right atrial pacing, RV pacing at optimal A-V delay (average 140 ± 22 ms, range 120-180 ms) resulted in significant DIVD reduction (59 ± 19 to 3 ± 22 ms, P < 0.001), and increase in LV stroke volume as measured by LV outflow tract velocity-time integral (14.9 ± 2.8 to 16.9 ± 3.0 cm, P < 0.001), along with enhanced global RV contractility and LV diastolic filling. CONCLUSION: Right-to-left ventricle resynchronization of the onset of diastolic relaxation results in stroke volume increase in CTEPH patients. Whether RV pacing may be a novel therapeutic target in RV failure following chronic pressure overload remains to be investigated.

Right-to-left ventricular diastolic delay in chronic thromboembolic pulmonary hypertension is associated with activation delay and action potential prolongation in right ventricle.

BACKGROUND: Delayed left ventricle (LV)-to-right ventricle (RV) peak shortening results in cardiac output reduction in patients with chronic thromboembolic hypertension (CTEPH) and other types of pulmonary arterial hypertension. Why the synchrony between LV and RV is lost is unknown. We hypothesized that RV electrophysiological remodeling, notably, conduction slowing and action potential prolongation, contribute to this loss in synchrony. METHODS AND RESULTS: We conducted epicardial mapping during pulmonary endarterectomy in 26 patients with CTEPH and compared these findings with clinical, hemodynamic, and echocardiographic variables. We consecutively placed a multielectrode grid on the epicardium of the RV free wall and LV lateral wall. These regions corresponded to RV and LV areas where echocardiographic Doppler sample volumes were placed to measure RV-to-LV diastolic interventricular delay. RV and LV epicardial action potential duration was assessed by measuring activation-recovery interval. Onset of diastolic relaxation of RV free wall with respect to LV lateral wall (diastolic interventricular delay) was delayed by 38+/-31 ms in patients with CTEPH versus -12+/-13 ms in control subjects (P<0.001), because, in patients with CTEPH, RV completed electric activation later than LV (65+/-20 versus 44+/-7 ms, P<0.001) and epicardial action potential duration, as assessed by activation-recovery interval measurement, was longer in RV free wall than in LV lateral wall (253+/-29 versus 240+/-22 ms, P<0.001). CONCLUSIONS: Additive effects of electrophysiological changes in RV, notably, conduction slowing and action potential prolongation, assessed by epicardial activation-recovery interval, contribute to diastolic interventricular delay in patients with CTEPH.

A novel echocardiographic predictor of in-hospital mortality and mid-term haemodynamic improvement after pulmonary endarterectomy for chronic thrombo-embolic pulmonary hypertension.

AIMS: To study whether pre-operative assessment, using echocardiography, of the timing of a particular feature in the pulmonary flow (pulmonary flow systolic notch) may predict in-hospital mortality and mid-term haemodynamic improvement after pulmonary endarterectomy (PEA) for chronic thrombo-embolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: Fifty-eight of 61 consecutive CTEPH patients (aged 53 +/- 14 years; 36 women) who underwent PEA between June 2002 and June 2005 were studied. Clinical, haemodynamic, and echocardiographic variables were assessed pre-operatively and at 3 months post-PEA. Timing of the notch was expressed as notch ratio (NR). Pre-operatively, seven patients had no notch, 33 had NR < 1.0, and 18 had NR > 1.0. NR was associated with in-hospital mortality (P < 0.01). Moreover, multivariable analysis revealed that among pre-operative variables, NR was an independent predictor of residual-increased pulmonary artery systolic pressure (>40 mmHg) at 3 months post-PEA (P = 0.01). Receiver operator characteristic analysis established NR = 1.0 as optimal cutoff to distinguish patients at risk of such unfavourable outcomes, with NR > 1.0 conferring higher risk. CONCLUSION: NR is related with in-hospital mortality and residual pulmonary hypertension after PEA. NR > 1.0 is associated with a higher risk of such unfavourable outcomes. NR may be considered a determinant of eligibility for PEA.

Sequence of echocardiographic changes during development of right ventricular failure in rat.

BACKGROUND: The temporal relations between the onset of echocardiographic changes and clinical diagnosis of right ventricular (RV) failure are unresolved. We have characterized such relations in a rat monocrotaline (MCT) model of RV failure. METHODS: Eight-week-old male Wistar rats were injected with MCT (60 mg/kg) or vehicle and underwent serial echocardiography. RV free-wall thickness (RVWT), pulmonary artery acceleration time normalized to cycle length (PAAT/CL), RV end-diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE) were measured. RESULTS: Significant differences in echocardiographic parameters between MCT-treated and control rats were found as early as 14 days before RV failure for RVWT, 10 days for PAAT/CL, and 7 days for RVEDD and TAPSE. The time intervals between the onset of changes in RVWT, PAAT/CL, RVEDD, and TAPSE and diagnosis of RV failure were 11.3 +/- 0.8, 10.9 +/- 0.7, 6.5 +/- 0.5, and 5.4 +/- 0.7 days, respectively. The sequence of echocardiographic changes was consistent in all animals during development of RV failure. CONCLUSIONS: Pulmonary hypertension (assessed by PAAT/CL) and RV free-wall thickening (characterized by RVWT) precede RV dilation and RV systolic dysfunction (measured by RVEDD and TAPSE, respectively). Echocardiographic analysis permits accurate determination of the stage of disease development in MCT-induced RV failure.

Double orifice mitral valve; a coincidental finding.

A double orifice mitral valve (DOMV) represents a rare congenital malformation characterised by two valve orifices with two separate subvalvular apparatus. This case demonstrates the necessity of careful imaging of the mitral valve apparatus, not only in patients with atrioventricular septal defects, but also in patients with congenital left obstructive heart disease.

Applicability of bosentan in Dutch patients with Eisenmenger syndrome: preliminary results on safety and exercise capacity.

BACKGROUND: The purpose of this study was to investigate the applicability of bosentan treatment in a broad selection of patients with Eisenmenger syndrome. METHODS: Dutch patients with Eisenmenger syndrome in New York Heart Association functional class III, 9 (41%) male and 13 (59%) female, including 11 patients with Down syndrome (50%), aged 20 to 61 years (median 37 years), were screened for an open-label, standardised treatment protocol. Patients underwent clinical examinations, six-minute walk test (6-MWT), resting oxygen saturation measurements, cardiac MRI, Doppler echocardiography, lung function tests and exercise capacity testing by peak oxygen consumption at baseline. At 12 weeks of treatment 6-MWT and at 26 weeks 6-MWT and Doppler echocardiography were repeated. RESULTS: Median follow-up of the patients who started bosentan treatment was five months (range 0.5 to 9.6 months). Oxygen saturation at baseline was 83% (range 76 to 91%) and did not decrease during treatment. Compared with baseline, 6-MWT increased after 12 weeks from 333±93 m to 384±89 m. None of the patients discontinued medication and no liver function abnormalities were observed. Of all Doppler echocardiographic and MRI parameters measured for right ventricular function, tricuspid annular peak systolic velocities using tissue Doppler imaging (TDI-S) was the only independent predictor for six-minute walk test (ß=0.8, p=0.001). CONCLUSION: Bosentan may be safely applied in patients with Eisenmenger syndrome combined with complex congenital heart disease or with Down syndrome. Our preliminary results suggest that exercise tolerance improves during the first months of bosentan treatment.

Hemodynamic effects of leg crossing and skeletal muscle tensing during free standing in patients with vasovagal syncope.

Physical maneuvers can be applied to abort or delay an impending vasovagal faint. These countermaneuvers would be more beneficial if applied as a preventive measure. We hypothesized that, in patients with recurrent vasovagal syncope, leg crossing produces a rise in cardiac output (CO) and thereby in blood pressure (BP) with an additional rise in BP by muscle tensing. We analyzed the age and gender effect on the BP response. To confirm that, during the maneuvers, Modelflow CO changes in proportion to actual CO, 10 healthy subjects performed the study protocol with CO evaluated simultaneously by Modelflow and by inert gas rebreathing. Changes in Modelflow CO were similar in direction and magnitude to inert gas rebreathing-determined CO changes. Eighty-eight patients diagnosed with vasovagal syncope applied leg crossing after a 5-min free-standing period. Fifty-four of these patients also applied tensing of leg and abdominal muscles. Leg crossing produced a significant rise in CO (+9.5%; P < 0.01) and thereby in mean arterial pressure (+3.3%; P < 0.01). Muscle tensing produced an additional increase in CO (+8.3%; P < 0.01) and mean arterial pressure (+7.8%; P < 0.01). The rise in BP during leg crossing was larger in the elderly.