Exercise hemodynamics during extended continuous flow left ventricular assist device support: the response of systemic cardiovascular parameters and pump performance.

Patients on continuous flow left ventricular assist devices (cf-LVADs) are able to return to an active lifestyle and perform all sorts of physical activities. This study aims to evaluate exercise hemodynamics in patients with a HeartMate II cf-LVAD (HM II). Thirty (30) patients underwent a bicycle exercise test. Along with exercise capacity, systemic cardiovascular responses and pump performance were evaluated at 6 and 12 months after HM II implantation. From rest to maximum exercise, heart rate increased from 87 ± 14 to 140 ± 32 beats/minute (bpm) (P<0.01), while systolic arterial blood pressure increased from 93 ± 12 to 116 ± 21 mm Hg (P<0.01). Total cardiac output (TCO) increased from 4.1 ± 1.1 to 8.5 ± 2.8 L/min (P<0.01) while pump flow increased less, from 5.1 ± 0.7 to 6.4 ± 0.6 L/min (P<0.01). Systemic vascular resistance (SVR) decreased from 1776 ± 750 to 1013 ± 83 dynes.s/cm(5) (P<0.001) and showed the strongest correlation with TCO (r= -0.72; P<0.01). Exercise capacity was affected by older age, while blood pressure increased significantly in men compared with women. Exercise capacity remained consistent at 6 and 12 months after HM II implantation, 51% ± 13% and 52% ± 13% of predicted VO2 max for normal subjects corrected for age and gender. In conclusion, pump flow of the HM II may contribute partially to TCO during exercise, while SVR was the strongest determinant of TCO.

Single-centre experience of 85 patients with a continuous-flow left ventricular assist device: clinical practice and outcome after extended support.

OBJECTIVES: We evaluated our single-centre clinical experience with the HeartMate II (HM II) left ventricular assist device (LVAD) as a bridge to transplantation (BTT) in end-stage heart failure (HF) patients. METHODS: Survival rates, echocardiographic parameters, laboratory values and adverse events of 85 consecutive patients supported with a HM II were evaluated. RESULTS: Overall, mean age was 45 ± 13 years, 62 (73%) were male and non-ischaemic dilatated cardiomyopathy was present in 60 (71%) patients. The median duration of mechanical support was 387 days (IQR 150-600), with a range of 1-1835 days. The 6-month, 1-, 2-, 3- and 4-year survival rates during HM II LVAD support were 85, 81, 76, 76 and 68%, respectively. Echocardiographic parameters demonstrated effective left ventricular unloading, while laboratory results reflected adequate organ perfusion. However, HM II support was associated with adverse events, such as infections in 42 patients (49%; 0.67 events/patient-year), cardiac arrhythmia in 44 (52%; 0.86 events/patient-year), bleeding complications in 32 (38%; 0.43 events/patient-year) and neurological dysfunction in 17 (20%; 0.19 events/patient-year). CONCLUSIONS: In view of the increasing shortage of donor hearts, HM II LVAD support may be considered a life-saving treatment in end-stage HF patients, with good survival. However, it is still associated with some serious adverse events, of which neurological complications are the most critical.

Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support.

AIMS: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and is emerging as a biomarker of cardiac remodelling. Left ventricular assist devices (LVADs) provide unloading of the left ventricle, resulting in partial reverse remodelling. Our aim was to study GDF-15 in patients with a non-ischaemic dilated cardiomyopathy (DCM) during LVAD support. METHODS AND RESULTS: We analysed circulating GDF-15 in 30 patients before and 1, 3, and 6 months after LVAD implantation and before heart transplantation or explantation. In addition, mRNA and protein expression of GDF-15 were evaluated in myocardial tissue obtained prior to and after LVAD support. Circulating GDF-15 was significantly higher before LVAD implantation as compared with healthy controls (P < 0.001). After 1 month of mechanical support, GDF-15 levels were significantly decreased compared with pre-implantation levels (P < 0.001) and remained stable thereafter. Circulating GDF-15 was significantly correlated with kidney function and the severity of myocardial fibrosis. Interestingly, GDF-15 mRNA and protein expression in the myocardium were hardly detectable. CONCLUSIONS: High circulating levels of GDF-15 in patients with end-stage non-ischaemic DCM correlate with myocardial fibrosis and kidney function and decline strongly after 1 month of mechanical unloading, remaining stable thereafter. However, cardiac mRNA and protein expression of GDF-15 are very low, suggesting that the heart is not an important source of GDF-15 production in these patients.

[Peripartum cardiomyopathy in young women]. / Peripartum-cardiomyopathie bij jonge vrouwen.

Two women aged 26 and 41 were diagnosed with peripartum cardiomyopathy (PPCM). They presented with shortness of breath and oedematous ankles. The first woman presented in her 37th week of pregnancy. Her father had had dilated cardiomyopathy. A caesarean section was carried out. Her left ventricular function declined and she was therefore treated by means of an Impella heart pump and later, a left-ventricular assisting device. She eventually underwent urgent heart transplantation and recovered. The second woman presented 6 weeks after having given birth to twins. She was treated with a diuretic, an ACE inhibitor, a beta blocker and recovered. PPCM is a rare and potentially life-threatening form of dilated cardiomyopathy with left-ventricular systolic dysfunction that affects women in late pregnancy or in the early puerperium. Its pathogenesis is poorly understood. The generation of a cardiotoxic prolactin subfragment appears to play a key role in the pathophysiology. PPCM is difficult to diagnose as the initial complaints may be interpreted as the normal physiologic changes of pregnancy. In addition, prior definitions emphasising strict time windows, the lack of awareness and the rarity of the full-blown disease have sometimes resulted in the condition being overlooked and misdiagnosed.

Should we optimize cardiac resynchronization therapy during exercise?

Should We Optimize CRT During Exercise? Cardiac resynchronization therapy aims at diminishing cardiac dyssynchrony in patients with heart failure. The effect of cardiac resynchronization therapy can be improved by optimization of the atrioventricular (AV) and interventricular (VV) delays. Currently, optimization of these pacing settings is mainly performed during resting conditions. This paper aims to objectively review the current literature about a rate-adaptive AV and VV delay in cardiac resynchronization therapy. The current evidence for a rate-adaptive AV and VV delay comprises only small nonrandomized studies on acute effects. The effect of exercise on the optimal AV delay was heterogeneous between studies. The optimal VV delay was influenced by exercise conditions in some, but not all patients. Possible explanations lie in the heterogeneous electrical and mechanical responses to exercise in patients with a complex disease such as heart failure with asynchronous contraction. Current evidence is insufficient to show the superiority of a rate-adaptive AV or VV delay in all CRT patients. Individualized exercise programming may be warranted in selected patients.

Sarcoid myocarditis with ventricular tachycardia mimicking ARVD/C.

Cardiac sarcoidosis (CS) is a multisystem granulomatous disorder of unknown etiology with frequent cardiac involvement. We describe a patient presenting with a ventricular tachycardia, presumably originating in the right ventricle (RV). This patient had a malignant clinical course with initial diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C); however, at postmortem histopathology revealed epithelioid granulomas with fibrosis localized in the interventricular septum, typical for sarcoidosis, without signs of extracardiac sarcoidosis. In conclusion, sarcoid myocarditis may present with signs and symptoms of ARVD/C and only histopathology can differentiate the 2 diseases. In the cases of atypical clinical presentation or when histopathological proof of ARVD is absent, a close follow-up is advisable to identify other potentially treatable disorders.

Practical and conceptual limitations of tissue Doppler imaging to predict reverse remodelling in cardiac resynchronisation therapy.

BACKGROUND: Recent, conflicting results about the use of tissue Doppler imaging derived (TDI-) asynchrony indices to predict reverse remodelling after cardiac resynchronisation therapy (CRT) have raised questions about their physiological meaning and methodological limitations. METHODS: In 41 patients, baseline TDI-derived septal to lateral delays of peak velocities (TDI-SL), standard deviation of peak velocities over 12 segments (Ts-SD), and peak 2D longitudinal strain (strain-SL) were compared with volumetric response (reduction in end-systolic volume of > or =15%) after at least 6 months of CRT. Timing of peak TDI velocities was compared to timing of 2DS velocities and strain-SL. Influence of sample position, transverse motion, and interobserver inconsistency of the chosen peak velocities was assessed. Diagnostic accuracy of TDI-based delays was compared to accuracy of visual and 2D strain-based assessment. RESULTS: After 7.0+/-3.2 months of CRT, 24 patients were classified as responders. TDI-SL and Ts-SD were similar between responders and nonresponders at baseline, did not predict response, and were unaffected by CRT. Visual asynchrony scoring and strain-SL were better predictors of response than TDI-SL and Ts-SD. TDI measurements were highly susceptible to sample location and transverse motion components and poorly correlated with the timing of longitudinal contraction. There was a considerably poor agreement between observers with regard to scoring of TDI-SL and Ts-SD. CONCLUSION: TDI-based measurements of asynchrony do not appear robust predictors of volume response to CRT.