Impact of glycemic and blood pressure variability on surrogate measures of cardiovascular outcomes in type 2 diabetic patients.

OBJECTIVE: The effect of glycemic variability (GV) on cardiovascular risk has not been fully clarified in type 2 diabetes. We evaluated the effect of GV, blood pressure (BP), and oxidative stress on intima-media thickness (IMT), left ventricular mass index (LVMI), flow-mediated dilation (FMD), and sympathovagal balance (low frequency [LF]/high frequency [HF] ratio) in 26 type 2 diabetic patients (diabetes duration 4.41±4.81 years; HbA1c 6.70±1.25%) receiving diet and/or metformin treatment, with no hypotensive treatment or complications. RESEARCH DESIGN AND METHODS: Continuous glucose monitoring (CGM) data were used to calculate mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA)-2, mean blood glucose (MBG), mean postprandial glucose excursion (MPPGE), and incremental area under the curve (IAUC). Blood pressure (BP), circadian rhythm, and urinary 15-F2t-isoprostane (8-iso-prostaglandin F2α [PGF2α]) were also evaluated. Subjects were divided into dipper (D) and nondipper (ND) groups according to ΔBP. RESULTS: IMT and LVMI were increased in ND versus D (0.77±0.08 vs. 0.68±0.13 [P=0.04] and 67±14 vs. 55±11 [P=0.03], respectively). MBG, MAGE, and IAUC were significantly associated with LF/HF ratio at night (r=0.50, P=0.01; r=0.40, P=0.04; r=0.41, P=0.04, respectively), MPPGE was negatively associated with FMD (r=-0.45, P=0.02), and CONGA-2 was positively associated with LVMI (r=0.55, P=0.006). The Δsystolic BP was negatively associated with IMT (r=-0.43, P=0.03) and with LVMI (r=-0.52, P=0.01). Urinary 8-iso-PGF2α was positively associated with LVMI (r=0.68 P<0.001). CONCLUSIONS: An impaired GV and BP variability is associated with endothelial and cardiovascular damage in short-term diabetic patients with optimal metabolic control. Oxidative stress is the only independent predictor of increased LV mass and correlates with glucose and BP variability.

Ventricular dyssynchrony: 12-month evaluation in ischemic versus nonischemic CRT patients.

OBJECTIVE: Few data exist about the potential differences in the dyssynchrony status of cardiac resynchronization therapy (CRT) candidates stratified by etiology of heart failure, and about the evolution of dyssynchrony at long-term follow-up. We provided a description of intra-ventricular dyssynchrony at baseline, 6 months and 12 months in ischemic and nonischemic CRT patients. METHODS: Tissue Doppler Imaging was performed in 35 CRT candidates (18 ischemic, 17 nonischemic) at baseline, and at 6-month and 12-month follow-up. A group of 11 healthy subjects was considered for comparison. RESULTS: At baseline, the standard deviation and the maximum activation delay between any 2 segments were significantly greater in ischemic (38+/-33ms, 94+/-76ms) and nonischemic (38+/-24ms, 96+/-62ms) patients versus controls (9+/-7ms, 22+/-15ms) (all p<0.05). The average time to activation for posterior and lateral wall was significantly higher in nonischemic patients, while the anterior septum activated later in ischemic patients. At 6-month follow-up, standard deviation and maximum delay did not vary in nonischemic while decreased in ischemic group. All changes persisted at 12 months. CONCLUSIONS: No baseline differences were observed between ischemic and nonischemic patients using studied indices. At 6- and 12-month follow-up, only ischemic patients presented a significant reduction in dyssynchrony values, although in both groups CRT did not lead to a complete normalization of LV synchronism.

Efficacy of LOw-dose DObutamine stress-echocardiography to predict cardiac resynchronization therapy response (LODO-CRT) multicenter prospective study: design and rationale.

BACKGROUND: Although cardiac resynchronization therapy (CRT) has a well-demonstrated therapeutic effect in selected patients with advanced heart failure on optimized drug therapy, nonresponder rate remains high. The LODO-CRT is designed to improve patient selection for CRT. Design and rationale of this study are presented herein. METHODS: LODO-CRT is a multicenter prospective study, started in late 2006, that enrolls patients with conventional indications for CRT (symptomatic stable New York Heart Association class III-IV on optimized drug therapy, QRS > or =120 milliseconds, left ventricular [LV] dilatation, LV ejection fraction < or =35%). This study is designed to assess the predictive value of LV contractile reserve (LVCR), determined through dobutamine stress echocardiography (defined as an LV ejection fraction increase >5 units), in predicting CRT response during follow-up. Assessment of CRT effects will follow 2 sequential phases: in phase 1, CRT response end point is defined as LV end-systolic volume reduction > or =10% at 6 months; in phase 2, both LV end-systolic volume reduction and clinical status via a clinical composite score will be evaluated at 12 months follow-up. Predictive value of LVCR will be compared to other measures, such as LV dyssynchrony measures, through adjusted multivariable analysis. For the purpose of the study, target patient number is 270 (with 95% confidence, 80% power, alpha < or = .05). Enrollment should be complete by the end of 2008. CONCLUSIONS: The LODO-CRT trial is testing the hypothesis that LVCR assessment, using low-dose dobutamine stress echocardiography test, should effectively predict positive response to CRT both in terms of the reverse remodeling process as well as favorable long-term clinical outcome. Moreover, the predictive value of LVCR will be compared to that of conventional intra-LV dyssynchrony measures.

Results of the SCART study: selection of candidates for cardiac resynchronisation therapy.

OBJECTIVE: To prospectively determine whether prespecified electrocardiographic, echocardiographic and tissue Doppler imaging (TDI) selection criteria may predict a positive response to cardiac resynchronisation therapy (CRT). METHODS: In this multicentre, prospective, non-randomised study, 96 heart failure patients with New York Heart Association class III-IV symptoms, an ejection fraction of < or =35%, and at least one marker of ventricular dyssynchrony according to prespecified electrocardiographic, echocardiographic or TDI criteria were enrolled. The primary endpoint was an improvement in the clinical composite score at 6 months. RESULTS: At enrolment, 70 patients fulfilled the electrocardiographic criterion (QRS duration > or =150 ms), 77 patients showed echocardiographic signs of dyssynchrony, and 37 patients met the TDI dyssynchrony criteria. The overall responder rate was 78/96 (81%). In particular, the primary endpoint was reached in 68 patients who fulfilled the echocardiographic criteria as compared with 10 patients who did not (88 vs. 53%, P = 0.001). The patients who met the echocardiographic criteria showed a significant greater reduction in left ventricular end-systolic diameter (P = 0.029) and a higher improvement in quality of life (P = 0.017) than patients who did not. Neither electrocardiographic nor TDI criteria seemed to predict a positive response to CRT. CONCLUSIONS: In our patient population, mechanical indexes of dyssynchrony as assessed by echocardiography appeared to identify CRT responders. Although TDI is useful for evaluating ventricular dyssynchrony after CRT, the prespecified TDI inclusion criteria adopted in this investigation did not increase the number of CRT responders.

Biventricular upgrading in patients with conventional pacing system and congestive heart failure: results and response predictors.

BACKGROUND: There are few studies on cardiac resynchronization therapy (CRT) in heart failure (HF) patients with preexisting right ventricular (RV) pacing. The purpose of this study was to determine the efficacy of CRT upgrading in RV-paced patients and the predictivity of electromechanical dyssynchrony parameters (EDP) evaluated by standard echocardiography (ECHO) and tissue Doppler imaging (TDI). METHODS: Thirty-eight consecutive patients with HF [New York Heart Association (NYHA) class III or IV, LVEF < 35%], prior continuous RV pacing, and absence of atrial fibrillation were enrolled in the presence of a paced QRS > or = 150 ms and evaluated by ECHO and TDI. A responder was defined as a patient with a favorable change in NYHA class and neither HF hospitalization nor death, plus an absolute increase of LVEF > or = 10 units. RESULTS: At six-months follow-up, the whole study population had significant improvement in symptoms, systolic function, and QRS duration (P < 0.001); 32 (84%) patients had a favorable clinical outcome, 25 (66%) were considered responders according to the previous definition. Postimplant QRS was similarly reduced in both responders and nonresponders, whereas EDP had a significant improvement only in responders (P < 0.05). Using EDP, 23 (79%) patients were responders compared with 2 (22%) patients without mechanical dyssynchrony (P = 0.002). CONCLUSIONS: In HF patients with previous RV pacing, CRT is effective to improve clinical, functional outcome, and LV performance and to reduce electromechanical dyssynchrony in a large proportion of patients. Dyssynchrony evaluated by standard and TDI ECHO can be useful for CRT selection of paced patients.

Left ventricular electromechanical delay in patients with heart failure and normal QRS duration and in patients with right and left bundle branch block.

AIMS: We sought to define the reference values of intra-left ventricular (LV) electromechanical delay (EMD), and to assess the prevalence (and pattern) of intra-LV dyssynchrony in patients with heart failure (HF) and normal QRS and in patients with right and left bundle branch block. METHODS AND RESULTS: We used tissue Doppler imaging echocardiography and a six-LV wall model to study LV EMD in 103 patients [41 with HF and normal QRS, 22 with right bundle branch block (RBBB), and 40 with left bundle branch block (LBBB)], and in 59 controls. In controls, the median intra-LV EMD was 17 ms, (inter-quartile range 13-30); 95% of controls had a value < or =41 ms. Patients showed a longer intra-LV EMD than controls: 33 ms (20-57) in patients with normal QRS, 32 ms (23-50) in RBBB patients, and 50 ms (30-94) in LBBB patients. Intra-LV dyssynchrony (defined as intra-LV EMD >41 ms) was present in 39, 36, and 60% of the patients, respectively. On average, HF patients showed the same pattern of activation as controls, from the septum to the posterior wall, but activation times were significantly prolonged. In RBBB patients the activation sequence was directed from inferior to anterior and in LBBB from anterior to inferior wall. CONCLUSIONS: Left ventricular dyssynchrony was present in several patients with HF and normal QRS, and in patients with RBBB; conversely, 40% of LBBB patients showed values of LV EMD within the normal range. Left ventricular activation sequence was different between groups. Assessment of LV synchronicity by means of imaging techniques may be more important than QRS duration or morphology in selecting patients for cardiac resynchronization treatment.

Prediction of response to cardiac resynchronization therapy: the selection of candidates for CRT (SCART) study.

BACKGROUND: The aim of this study was to evaluate the ability of baseline clinical and echocardiographic parameters to predict a positive response to CRT. METHODS: We analyzed 6-month data from the first 133 consecutive patients enrolled in a multicenter prospective study. These patients had symptomatic heart failure (HF) refractory to pharmacological therapy (NYHA class II-IV), left ventricular ejection fraction (LVEF) < or =35%, and prespecified electrocardiographic, echocardiographic or tissue Doppler imaging markers of left ventricular (LV) dyssynchrony. RESULTS: After a follow-up period of 6 months, 1 patient died and 13 were hospitalized for worsening HF. There were significant (P < 0.01) clinical, functional, and echocardiographic improvements that included: New York heart Association Class, Quality-of-Life Score, QRS duration, LVEF, LV end-diastolic and end-systolic diameter (LVESD), and severity of mitral regurgitation A positive response was documented in 90/133 (68%) patients who presented an improved clinical composite score associated to an increase in LVEF > or = 5 units. A multivariate analysis identified that a smaller LVESD (OR = 0.957, 95% CI 0.920-0.996; P = 0.030) and longer interventricular mechanical delay (IVMD) (OR = 1.017, 95% CI 1.005-1.029, P = 0.007) as independent predictors of a positive response. Receiver-operating curve analysis showed that a positive response to CRT may be predicted in patients with IVMD > 44 ms (with a sensitivity of 66% and a specificity of 55%) or with LVESD < 60 mm (with a sensitivity of 66% and a specificity of 61%). CONCLUSIONS: Our results confirm the limited value of QRS duration in the selection of patients for CRT. A less-advanced stage of disease and echocardiographic evidence of interventricular dyssynchrony demonstrated to predict response to CRT, while intraventricular dyssynchrony did not predict response.

Effects of right ventricular pacing on intra-left ventricular electromechanical activation in patients with native narrow QRS.

Some patients with right ventricular (RV) apical pacing show contractile asynchrony of the left ventricle. Whether the asynchrony is due to RV pacing or was a preexistimg condition remains unknown. The aim of this study was to evaluate how much pacing from the RV apex affects left ventricular (LV) electromechanical activation and to assess whether the extent of LV asynchrony during RV pacing can be predicted by clinical, electrocardiographic, or echocardiographic findings obtained during spontaneous rhythm. We evaluated 56 patients with narrow QRS and preserved atrioventricular conduction who received permanent backup RV pacing. Intra-LV electromechanical activation was assessed during spontaneous rhythm and during pacing using tissue Doppler echocardiography. An abnormal intra-LV electromechanical delay (EMD) (defined as a >41-ms difference between the faster and slower activated LV wall) was found in 15 patients (27%) during spontaneous rhythm and 28 patients (50%) during RV pacing (p<0.001). Of the 9 baseline variables (age, gender, history of heart failure, QRS duration in spontaneous rhythm and during pacing, LV end-diastolic and end-systolic diameters, LV ejection fraction, and intra-LV EMD in spontaneous rhythm), an abnormal baseline intra-LV EMD and QRS duration of >85 ms were independent predictors of an abnormal intra-LV delay during RV pacing. RV apical pacing induces asynchrony of LV contractions in a substantial percentage of patients but not in all. Although normal baseline intra-LV electromechanical activation cannot exclude the development of significant asynchrony during RV pacing, the presence of preimplant LV asynchrony predicts for a worsening of this detrimental effect.

Long-term effectiveness of dual site left ventricular cardiac resynchronization therapy in a patient with congestive heart failure.

This article describes a case of cardiac resynchronization therapy (CRT) performed with dual site left ventricular pacing. The main clinical and functional long-term results are in agreement with the most recent data regarding traditional CRT. Furthermore, this innovative pacing modality allowed optimal inter- and intraventricular resynchronization.