Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms.

AIM: To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS: A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION: CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

Maternal cardiovascular impairment in pregnancies complicated by severe fetal growth restriction.

Fetal growth restriction and preeclampsia are both conditions of placental etiology and associated to increased risk for the long-term development of cardiovascular disease in the mother. At presentation, preeclampsia is associated with maternal global diastolic dysfunction, which is determined, at least in part, by increased afterload and myocardial stiffness. The aim of this study is to test the hypothesis that women with normotensive fetal growth-restricted pregnancies also exhibit global diastolic dysfunction. This was a prospective case-control study conducted over a 3-year period involving 29 preterm fetal growth-restricted pregnancies, 25 preeclamptic with fetal growth restriction pregnancies, and 58 matched control pregnancies. Women were assessed by conventional echocardiography and tissue Doppler imaging at diagnosis of the complication and followed-up at 12 weeks postpartum. Fetal growth-restricted pregnancies are characterized by a lower cardiac index and higher total vascular resistance index than expected for gestation. Compared with controls, fetal growth-restricted pregnancy was associated with significantly increased prevalence (P<0.001) of asymptomatic left ventricular diastolic dysfunction (28% versus 4%) and widespread impaired myocardial relaxation (59% versus 21%). Unlike preeclampsia, cardiac geometry and intrinsic myocardial contractility were preserved in fetal growth-restricted pregnancy. Fetal growth-restricted pregnancies are characterized by a low output, high resistance circulatory state, as well as a higher prevalence of asymptomatic global diastolic dysfunction and poor cardiac reserve. These findings may explain the increased long-term cardiovascular risk in these women who have had fetal growth-restricted pregnancies. Further studies are needed to clarify the postnatal natural history of cardiac dysfunction in these women.

Severe myocardial impairment and chamber dysfunction in preterm preeclampsia.

OBJECTIVE: The long-term cardiovascular risk of preeclampsia is known to be significantly higher in women requiring preterm delivery before 37 weeks compared with those delivered at term. The aim of this study is to assess and compare maternal cardiac function and geometry in acute preterm and term preeclampsia. METHODS: This is a prospective case-control study of 27 preterm and 50 term preeclampsia and 104 matched controls assessed by conventional echocardiography and tissue Doppler imaging. RESULTS: Preeclampsia is associated with biventricular diastolic dysfunction, altered geometry, and widespread myocardial impairment. However, only preterm but not term preeclampsia is characterized by biventricular systolic dysfunction (26% vs. 4%; p < 0.05) and severe left ventricular hypertrophy (19% vs. 2%; p < 0.05). CONCLUSIONS: Women with preterm preeclampsia have a more severe cardiac impairment than those with term preeclampsia. This finding may explain the increased long-term cardiovascular risk associated with preterm preeclampsia. The cardiac assessment of women with preterm preeclampsia may be of relevance in identifying women at higher risk of developing cardiovascular morbidity and mortality in later life.

Preeclampsia is associated with persistent postpartum cardiovascular impairment.

Preeclampsia is associated with asymptomatic global left ventricular abnormal function and geometry during the acute phase of the disorder. These subclinical abnormalities in cardiac findings are known to be important in cardiovascular risk stratification for nonpregnant patients. Furthermore, epidemiological studies have also demonstrated a relationship between preeclampsia and cardiac morbidity and mortality later in life. The aim of this study was to evaluate the postpartum natural history and clinical significance of asymptomatic left ventricular impairment known to occur with acute preeclampsia. This was a prospective longitudinal case-control study of 64 subjects with preeclampsia and 78 matched controls. There were 3 time point assessments, pregnancy and 1 and 2 years postpartum. The assessments included a medical and family history, blood pressure profile, echocardiography, and 12-lead ECG. At 1 year postpartum, asymptomatic left ventricular moderate-severe dysfunction/hypertrophy was significantly higher in preterm preeclampsia (56%) compared with term preeclampsia (14%) or matched controls (8%; P values <0.001). The risk of developing essential hypertension within 2 years was significantly higher in both preterm preeclamptic women and those with persistent left ventricular moderate-severe abnormal function/geometry. The cardiovascular implications of preeclampsia do not end with the birth of the infant and placenta. The majority of preterm preeclamptic women have stage B asymptomatic heart failure postpartum, and 40% develop essential hypertension within 1 to 2 years after pregnancy. Women with a history of preterm preeclampsia may benefit from formal cardiovascular risk assessment in the 1 to 2 years after delivery to identify those who would benefit from targeted therapeutic intervention.

Maternal cardiac dysfunction and remodeling in women with preeclampsia at term.

Preeclampsia is a disease associated with significant cardiovascular morbidity during pregnancy and in later life. This study was designed to evaluate cardiac function and remodeling in preeclampsia occurring at term. This was a prospective case-control study of 50 term preeclampsia and 50 normal pregnancies assessed by echocardiography and tissue Doppler analysis. Global diastolic dysfunction was observed more frequently in preeclampsia versus control pregnancies (40% versus 14%, P = 0.007). Increased cardiac work and left ventricular mass indices suggest that left ventricular remodeling was an adaptive response to maintain myocardial contractility with preeclampsia at term. Approximately 20% of patients with preeclampsia at term have more evident myocardial damage. Diastolic dysfunction usually precedes systolic dysfunction in the evolution of ischemic or hypertensive cardiac diseases and is of prognostic value in the prediction of long-term cardiovascular morbidity. The study findings also have significant implications for the acute medical management of preeclampsia.