Acute echocardiographic optimization of multiple stimulation configurations of cardiac resynchronization therapy through quadripolar left ventricular pacing: a tailored approach.

BACKGROUND: Cardiac resynchronization therapy (CRT) is ineffective in approximately 30% of recipients, in part due to sub-optimal left ventricular (LV) pacing location. The Quartet LV lead, with 2 additional electrodes proximal to conventional bipolar lead electrodes, enables 10 different pacing configurations at four independent LV locations. In a CRT patient cohort, we sought to evaluate the spectrum of echocardiographic and electrocardiographic response over these 10 configurations, to select the optimal one in each patient. Moreover, we sought to evaluate the 6-months clinical and echocardiographic response to a "tailored approach" in which the optimal LV pacing configuration for CRT was determined by echocardiographic measures, QRSd and pacing capture thresholds. METHODS: Twenty-two consecutive CRT indicated patients were implanted with a quadripolar CRT system (St. Jude Medical). Optimal LV pacing configuration was determined by echocardiographic measures, including velocity time integral (VTI), myocardial performance index (MPI) and mitral regurgitation (MR), and an electrocardiographic measure (QRS duration) during pacing from each of the configurations at pre-discharge. The optimal LV pacing vector was chosen for every patient. Clinical and echocardiographic assessment was repeated after 6 months. RESULTS: Various configurations provided different VTI, MPI, MR and QRSd values. Conventional bipolar vectors (ie, D1-M2, D1-RVc, M2-RVc) were rarely associated with the best echocardiographic improvements and provided significantly worse VTI, MR, MPI, and QRSd values than the best configuration for every patient (P = .005, P = .05 and P = .03 for VTI; P = .01, P = .005 and P = .001 for MPI; P = .003, P = .01 and P = .005 for MR, P > .5, P = .01 and P = .05 for QRSd) Conversely, "unconventional" proximal configurations (ie, making use of P4 and M3 electrodes) were generally characterized by higher acute VTI, MR and MPI improvements. CRT devices were reprogrammed with an "unconventional" LV pacing configuration in 50% of patients. A significant improvement in New York Heart Association class (81%), LV ejection fraction (76%), end-diastolic and end-systolic volumes was observed after 6 months (P = .02, P < .001, P = .02 and P = .003, respectively). CONCLUSIONS: In this study, conventional bipolar vectors of quadripolar-CRT were rarely associated with the best echocardiographic improvements. Quadripolar CRT utilizing optimal LV pacing configuration was associated with a significant improvement in New York Heart Association class and LV ejection fraction after 6 months.

Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling.

OBJECTIVES: This study evaluated the safety, efficacy, and effect of MitraClip treatment on symptoms and left ventricular (LV) remodeling in nonresponders to cardiac resynchronization therapy (CRT). BACKGROUND: Moderate to severe functional mitral regurgitation (FMR) frequently persists after CRT, contributing to reduced or no response to CRT. Percutaneous repair with the MitraClip has been proposed as an additional therapeutic option in select patients with significant FMR. METHODS: Fifty-one severely symptomatic CRT nonresponders with significant FMR (grade ≥2, 100%) underwent MitraClip treatment. Changes in New York Heart Association functional class, degree of FMR, LV ejection fraction (EF), and LV end-diastolic/end-systolic volumes (EDV/ESV) before and after (3, 6, and 12 months) MitraClip implantation were recorded. Mortality data, including cause of death, were collected. RESULTS: MC treatment was feasible in all patients (49% 1 clip, 46% 2 clips). There were 2 periprocedural deaths. Median follow-up was 14 months (25th to 75th percentile: 8 to 17 months). New York Heart Association functional class improved acutely at discharge (73%) and continued to improve progressively during follow-up (regression model, p < 0.001). The proportion of patients with significant residual FMR (grade ≥2) progressively decreased during follow-up (regression model, p < 0.001). Reverse LV remodeling and improved LVEF were detected at 6 months, with further improvement at 12 months (regression model, p = 0.001, p = 0.008, and p = 0.031 for ESV, EDV, and LVEF, respectively). Overall 30-day mortality was 4.2%. Overall mortality during follow-up was 19.9 per 100 person-years (95% confidence interval: 10.3 to 38.3). Nonsurvivors had more compromised clinical baseline conditions, longer QRS duration, and a more dilated heart. CONCLUSIONS: FMR treatment with the MitraClip in CRT nonresponders was feasible, safe, and demonstrated improved functional class, increased LVEF, and reduced ventricular volumes in about 70% of these study patients.

Early diagnosis of left ventricular diastolic dysfunction in diabetic patients: a possible role for natriuretic peptides.

BACKGROUND: The aim of the present study was to verify whether BNP might detect pre-clinical diastolic dysfunction (LVDD) in type-2 diabetic patients. METHODS: One-hundred and twenty-seven consecutive outpatients with type-2 diabetes mellitus were enrolled into the study. Subjects with overt heart failure or NYHA class > 1, history of coronary artery disease, severe valvulopathy or chronic atrial fibrillation were excluded from the study. All patients underwent clinical evaluation, laboratory assessment of brain natriuretic peptide (BNP) and echocardiographic examination. RESULTS: No patients showed systolic impairment of left ventricular function, whereas diastolic dysfunction was detected in 53 (42%) cases (all impaired relaxation). Median BNP was 27 pg/ml without any significant difference between 76 patients with normal left ventricular function and 53 with diastolic dysfunction; in 54 (43%) patients showing HBA1C≥8 (uncontrolled diabetes) normal function was found in 32 and diastolic dysfunction in 22, with a significant difference of BNP at multivariate analysis (OR = 1.02, 95%CI = 1.05-1.09, p = 0.003). In uncontrolled diabetic cohort, BNP was a strong predictor for LVDD (OR = 2.7, 95%CI = 1.3-5.6, p = 0.006) along with the duration of diabetes (OR = 1.6, 95%CI = 1.1-2.9, p = 0.046). BNP > 25 pg/ml was a cut-off value with high accuracy to detect a LVDD. DISCUSSION: Early screening of high-risk patients for diabetic cardiomyopathy development might be useful to better control glycemic profile in order to reduce heart disease progression or even to reverse it CONCLUSIONS: BNP could be a cheap, easy and useful tool to screen those ones with preclinical ventricular diastolic dysfunction in a subset of patients particularly prone to develop cardiovascular complications, like uncontrolled diabetic patients.

Accuracy of N-terminal pro-brain natriuretic peptide in the identification of left ventricular dysfunction in high-risk asymptomatic patients.

OBJECTIVE: The role of natriuretic peptides in the screening of left ventricular dysfunction is still unclear. The aim of this study was to assess the usefulness of N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement in asymptomatic patients at high risk of developing left ventricular dysfunction. METHODS: One hundred and thirty-four consecutive ambulatory patients (mean age 56.1 +/- 7 years) were studied and selected on the basis of a history of hypertension of at least 5 years. Systolic dysfunction was defined as an ejection fraction of 45% or less. Statistical analysis was performed by both parametric and nonparametric approaches. Diagnostic accuracy was evaluated by receiver operating characteristic analysis. RESULTS: Echocardiography showed normal left ventricular function in 40 patients, diastolic dysfunction in 80 patients and systolic dysfunction in 14 patients. NT-proBNP levels were significantly higher in patients with systolic dysfunction (356.1 +/- 294.8 vs. 85.2 +/- 85.8 pg/ml; P < 0.05). Receiver operating characteristic analysis showed a high value of the area under the curve (0.89) for the detection of systolic dysfunction with a sensitivity of 83% and a specificity of 80% for a cut-off value of 114 pg/ml and with a negative predictive value of 0.98. CONCLUSION: In asymptomatic patients at high risk for heart failure because of a history of hypertension, the measurement of NT-proBNP levels may represent a useful screening test for left ventricular systolic dysfunction. Therefore, more expensive examinations, such as echocardiography, may be restricted only to patients with higher NT-proBNP levels.

Activity monitoring in heart failure patients with cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional capacity in heart failure patients. This study aimed to prospectively analyze long-term device-based monitoring of physical activity in patients undergoing CRT. METHODS AND RESULTS: The Activity Log Index (ALI), calculated by CRT devices, represents the percentage of time when acceleration exceeds a threshold and monitors the physical activity. Data from 178 CRT patients (New York Heart Association III 91%, left ventricular ejection fraction 21+/-6%, left ventricular end-diastolic diameter 69+/-9 mm, QRS 159+/-27 ms, sinus rhythm 81%) were retrieved. The ALI increased from a baseline value of 3.6+/-2.0 to 11.2+/-4.6 (p<0.005) 104 weeks after initiation of CRT. A plateau was reached at approximately 12 weeks and thereafter ALI remained stable for up to 2 years. The magnitude of the changes in ALI was similar in patients with different etiologies and underlying rhythms. Despite similar values at baseline, elderly patients (>or=65 years) exhibited significantly lower ALI values than younger patients during the follow-up and at the plateau (9.5+/-4.2 vs 13.3+/-4.8, p<0.001). CONCLUSIONS: Device-based monitoring of physical activity in CRT patients is feasible. CRT resulted in a large and long-term increase in physical activity.

Surface expression of fractalkine receptor (CX3CR1) on CD4+/CD28 T cells in RA patients and correlation with atherosclerotic damage.

Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. Fractalkine, a CX3C/chemokine (CX3CL1), mediates monocytes-macrophage infiltration in activated endothelium, suggesting its specific role in atherosclerosis-related inflammation. In this study, we evaluate the following in early RA patients: the expression of fractalkine receptor (CX3CR1) on CD4+/CD28- T cells, a subset involved in atherosclerotic infiltration; the correlation between this subset and validated markers of early atherosclerosis. CD4+ T cells were isolated by immunomagnetics beads in 50 early RA patients and 26 healthy controls (HC). After isolation, CD4+/CD28-/CX3CR1+ T lymphocytes were assessed by FACS analysis. Endothelial dysfunction was evaluated by both carotid intima-media thickness (IMT) and flow-mediated vasodilation (FMV). We observed: a higher expansion of CD4+/CD28- subset in RA patients when compared to HC (7.7%, 5.15-9.7 vs. 0.7%, 0.2-1.5, P < 0.01; respectively); this expansion directly correlated with increased IMT (0.91 mm, 0.5-1.3 vs. 0.7 mm, 0.2-1, P < 0.01; RA vs. C, respectively) and inversely correlated with FMV (3.5%, 1.7-7 vs. 9%, 3.5-11, P < 0.01; RA vs. C, respectively); the large majority of CD4+/CD28-, in RA, coexpressed CX3CR1 (93%, 67-99 vs. 30%, 10-48, P < 0.01; RA vs. C, respectively); this expansion significantly correlated with both the parameters of premature vascular damage and DAS 28. Our data suggest that CX3CL1/CX3CR1 axis might play a role in the induction and development of the endothelial dysfunction during RA.

Measurements of mechanical asynchrony in patients with heart failure: is the puzzle completed?

Numerous randomized clinical trials demonstrated the beneficial effects of cardiac resynchronization therapy (CRT) in the treatment of moderate to severe heart failure. Despite careful patient selection, there is still a percentage of non-responders, that is as high as 30-50%. Patients are selected mainly on electrocardiogram criteria. Recent studies have observed that the severity of mechanical systolic asynchrony is a much better predictor of a response after CRT. Echocardiography allows a non-invasive evaluation atrioventricular and inter- and intraventricular synchrony; furthermore, recent advances have provided direct evidence of wall motion resynchronization in patients receiving CRT. Nevertheless, although many authors tried to search for the best echocardiographic index to identify systolic asynchrony, and consequently responders to CRT before the procedure, this issue is still a matter of debate. Our aim was to make an updated review of the more recent studies on this topic.

Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation.

OBJECTIVES: The goal of this study was to investigate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with permanent atrial fibrillation (AF) and the role of atrioventricular junction (AVJ) ablation. BACKGROUND: Cardiac resynchronization therapy has been proven effective in heart failure patients with sinus rhythm (SR). However, little is known about the effects of CRT in heart failure patients with permanent AF. METHODS: Efficacy of CRT on ventricular function, exercise performance, and reversal of maladaptive remodeling process was prospectively compared in 48 patients with permanent AF in whom ventricular rate was controlled by drugs, thus resulting in apparently adequate delivery of biventricular pacing (>85% of pacing time), and in 114 permanent AF patients, who had undergone AVJ ablation (100% of resynchronization therapy delivery). The clinical and echocardiographic long-term outcomes of both groups were compared with those of 511 SR patients treated with CRT. RESULTS: Both SR and AF groups showed significant and sustained improvements of all assessed parameters (model p < 0.001 for all parameters). However, within the AF group, only patients who underwent ablation showed a significant increase of ejection fraction (p < 0.001), reverse remodeling effect (p < 0.001), and improved exercise tolerance (p < 0.001); no improvements were observed in AF patients who did not undergo ablation. CONCLUSIONS: Heart failure patients with ventricular conduction disturbance and permanent AF treated with CRT showed large and sustained long-term (up to 4 year) improvements of left ventricular function and functional capacity, similar to patients in SR, only if AVJ ablation was performed.

Should sports activity be encouraged or contraindicated in hypertensive subjects?

Hypertension is considered one of the major risk factors for cardiovascular disease. There are a number of different approaches to the prevention, control and treatment of hypertension. One of these provides lifestyle modification as a means to facilitate drug step-down or drug withdrawal in hypertensive patients subjected to a pharmacological treatment, but also as a means to control blood pressure and reduce the risk of developing hypertension in subjects that have abnormal blood pressure but are not candidates for drug therapy. Lifestyle modification includes physical activity, and there is an ever-increasing amount of evidence that physical activity can modify the history of hypertension, acting as a reducer either of blood pressure or of the other cardiovascular risk factors. The aim of this article was to analyse the effects of exercise on blood pressure (neuro-hormonal, hormonal and vessel effects), illustrate which are the influences of age and gender on exercise-induced reduction of blood pressure, indicate how much exercise (in terms of intensity, frequency and duration) is required to induce positive modification of blood pressure and evaluate current Italian criteria for sports ability in athletes with hypertension.

Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure.

OBJECTIVES: This study sought to report long-term changes of cardiac autonomic control by continuous, device-based monitoring of the standard deviation of the averages of intrinsic intervals in the 288 five-min segments of a day (SDANN) and of heart rate (HR) profile in heart failure (HF) patients treated with cardiac resynchronization therapy (CRT). BACKGROUND: Data on long-term changes of time-domain parameters of heart rate variability (HRV) and of HR in highly symptomatic HF patients treated with CRT are lacking. METHODS: Stored data were retrieved for 113 HF patients (New York Heart Association functional class III to IV, left ventricular ejection fraction < or =35%, QRS >120 ms) receiving a CRT device capable of continuous assessment of HRV and HR profile. RESULTS: The CRT induced a reduction of minimum HR (from 63 +/- 9 beats/min to 58 +/- 7 beats/min, p < 0.001) and mean HR (from 76 +/- 10 beats/min to 72 +/- 8 beats/min, p < 0.01) and an increase of SDANN (from 69 +/- 23 ms to 93 +/- 27 ms, p < 0.001) at three-month follow-up, which were consistent with improvement of functional capacity and structural changes. Different kinetics were observed among these parameters. The SDANN reached the plateau before minimum HR, and mean HR was the slowest parameter to change. Suboptimal left ventricular lead position was associated with no significant functional and structural improvement as well as no change or even worsening of HRV. The two-year event-free survival rate was significantly lower (62% vs. 94%, p < 0.005) in patients without any SDANN change (Delta change < or =0%) compared with patients who showed an increase in SDANN (Delta change >0%) four weeks after CRT initiation. CONCLUSIONS: Cardiac resynchronization therapy is able to significantly modify the sympathetic-parasympathetic interaction to the heart, as defined by HR profile and HRV. Lack of HRV improvement four weeks after CRT identifies patients at higher risk for major cardiovascular events.

Chlamydia pneumoniae infection is associated with coronary artery disease but not implicated in inducing plaque instability.

BACKGROUND: Many authors have shown an association between Chlamydia pneumoniae (C. pneumoniae) infection and coronary artery disease. However, whether C. pneumoniae infection plays an important role in triggering an acute coronary event remains to be elucidated. METHODS: Sixty-four consecutive patients with unstable angina (group A), 56 consecutive patients with stable exertional angina (group B) and 74 control subjects (group C) were studied. The IgM, IgG and IgA anti-C. pneumoniae titers were assessed (microimmunofluorescence test Labsystem), values > or =1:16, > or =1:32 and > or =1:16 being respectively considered positive. RESULTS: IgM antibodies were found in 10.9% of group A and 12.5% of group B patients, whereas no subject of group C showed IgM titers (A vs. B, p=ns; C vs. A and B, p<0.05). Positive IgG titers were found in 76.6%, 82% and 44.6% in groups A, B and C, respectively (A vs. B, p=ns; C vs. A and B, p<0.05). Positive IgA titers were found in 62.5%, 61% and 31.1% in groups A, B and C, respectively (A vs. B, p=ns; C vs. A and B, p<0.05). Acute infection was observed in 10.9% and 12.5% of patients in groups A and B, respectively (p=ns); reinfection in 17% and 11%; no patient of the control group had signs of acute infection or reinfection. Chronic infection was observed in 34.4% and 37.5% in group A and B, respectively (p=ns). CONCLUSION: C. pneumoniae infection is associated with coronary artery disease, but no difference in serology is present between unstable and stable angina. Therefore, it does not seem implicated in triggering an acute coronary event.

Gender differences in the outcome of noninvasive cardiovascular treatment.

Cardiovascular diseases are equally common in both sexes with differences in pathogenesis, clinical presentation and outcome. The incidence of cardiovascular diseases progressively increases in women after the menopause and their development is related to risk factors and their interaction with the female hormones. The prognosis after myocardial infarction is worse in women because of a more difficult diagnosis (atypical symptoms, unclear ECG abnormalities) and because of social and economic factors. The role of hormone replacement therapy in atherosclerosis prevention is not yet clear, and there are many doubts about its administration because of the increased risk of breast cancer and cardiovascular events. Our best weapons against cardiovascular diseases are primary prevention and pharmacological therapy. The biological and pathophysiological mechanisms related to estrogen deficiency that may lead to the development of atherosclerosis are still unknown. Therefore, it would be useful to investigate the pathophysiology of atherosclerosis in women in order to improve primary prevention and the diagnostic and therapeutic strategies.