Left Ventricular Systolic Dysfunction In Patients Research Articles

Relation of baseline plasma phospholipid transfer protein (PLTP) activity to left ventricular systolic dysfunction in patients referred for coronary angiography

Phospholipid transfer protein (PLTP) is an important modulator of phospholipid transfer and exchange among proteins. It also plays a role in inflammation and oxidative stress. Accordingly, PLTP has been implicated in the development of atherosclerosis. Left ventricular (LV) systolic dysfunction is common in patients with atherosclerosis, and both inflammation and oxidative stress have also been implicated in its development and progression. The goal of the present study was to examine the relation between plasma PLTP activity and LV systolic function. Baseline plasma PLTP activity was measured in 389 male patients referred for coronary angiography for a variety of indications. Detailed clinical, angiographic and laboratory characteristics were available for the patients. Compared to those patients with normal LV function (defined as an ejection fraction of ≥55% on ventriculography), patients with any degree of LV dysfunction had elevated PLTP activity (median PLTP 17.8 pmol/μl/h versus 15.9 pmol/μl/h, p = 0.0038). Using multivariate analysis, and adjusting for a variety of confounding variables known to affect both LV function and PLTP activity, PLTP activity was an independent predictor of the presence of any left ventricular systolic dysfunction in the entire population (OR 1.47, 95% CI 1.12–1.93, p = 0.0052). Furthermore, PLTP activity was an independent predictor of the presence of LV dysfunction in both patients with and without myocardial infarction on presentation (OR 2.39, 95% CI 1.18–4.86, p = 0.0161 and OR 1.41, 95% CI 1.05–1.89, p = 0.0206, respectively). In conclusion, PLTP activity may represent a novel marker of LV systolic dysfunction in patients with known or suspected coronary artery disease.

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. This study sought to investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes that could predispose to AF. Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period (ERP) (209 +/- 8 ms; 52 cells, 18 patients vs 233 +/- 7 ms; 134 cells, 49 patients; P <0.05); confirmed by multiple linear regression analysis. The left ventricular ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36% +/- 4%, n = 15) than in those without LVSD (62% +/- 2%, n = 31; P <0.05). In cells from patients with LVEF <or= 45%, the ERP and action potential duration at 90% repolarization were shorter than in those from patients with LVEF > 45%, by 24% and 18%, respectively. The LVEF and ERP were positively correlated (r = 0.65, P <0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current were unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF.

Left ventricular diastolic dysfunction in normotensive diabetic patients in various age strata

Although patients with type 2 diabetes demonstrate cardiac diastolic dysfunction, it is well known that cardiac diastolic dysfunction is produced by hypertension and aging. The purpose of the present study was to elucidate the cardiac structure and function in normotensive patients with type 2 diabetes in various age strata in order to assess the effect of diabetes mellitus itself on cardiac function. Echocardiographic examination was performed in 77 normotensive patients with type 2 diabetes (age: 63 ± 11 years) and 76 healthy control subjects (age: 60 ± 11 years) who were in their forties, fifties, sixties, and seventies. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling ( E velocity) and the peak velocity of atrial filling ( A velocity), and the ratio of E to A ( E/ A) using the transmitral flow velocity, which were obtained by Doppler echocardiography. No difference was observed in the relative wall thickness, LV mass index, or LVEF between the diabetic patients and control subjects in any of the age strata. The E/ A ratio in the patients with type 2 diabetes was not different from that in the control subjects in their 40s (1.17 ± 0.35 versus 1.20 ± 0.36). However, E/ A was significantly lower in the diabetic patients than in the control subjects in their 50s (0.87 ± 0.28 versus 1.14 ± 0.24), 60s (0.78 ± 0.22 versus 0.97 ± 0.27), and 70s (0.66 ± 0.19 versus 0.84 ± 0.21) ( p < 0.05). The duration of type 2 diabetes was significantly longer in patients in their 50s (7.0 ± 2.5 years), 60s (8.0 ± 3.2 years), and 70s (10.4 ± 3.2 years) than in patients in their 40s (3.3 ± 1.9 years) ( p < 0.001). The value of E/ A in the diabetic patients correlated with the duration of type 2 diabetes ( r = −0.62, p < 0.001). These results indicate that cardiac diastolic dysfunction without LV systolic dysfunction in patients with well-controlled type 2 diabetes is related neither to hypertension nor LV hypertrophy, but rather to aging and the duration of type 2 diabetes.

The emerging role of PDE5 inhibition in heart failure

Background Heart failure (HF) is frequently associated with dysregulation of nitric oxide-mediated vascular tone. In HF patients with left ventricular systolic dysfunction (LVSD), right ventricular (RV) performance is an important determinant of exercise capacity and prognosis. Abnormal regulation of pulmonary vascular tone in these patients can lead to an increase in RV afterload and diminished function at rest and with exercise. The increased pulmonary vasomotor tone in HF patients is responsive to nitric oxide (NO), as administration of inhaled NO to patients with LVSD reduces pulmonary vascular resistance (PVR) and increases cardiac index (CI). As these beneficial effects of inhaled NO persist only briefly after cessation of its administration technically challenging to administercontinuously to ambulatory patients, the hydrolysis of its second messenger in vascular smooth muscle cells, cGMP, is an alternative target for pharmacologic augmentation through inhibition of phosphodiesterases (PDEs) responsible for its catabolism. Selective inhibition of Type 5 PDE, the predominant PDE isoform responsible for hydrolysis of cGMP in the lungs has been shown to lower resting PVR and pulmonary capillary wedge pressure (PCWP) and increase CI without causing systemichypotension in LVSD patients

A report of cardiac events in a phase II clinical study using trastuzumab combined with pertuzumab in HER2-positive metastatic breast cancer (MBC)

1028 Background: T and P are humanized recombinant monoclonal antibodies (MoAB) that target different epitopes of HER2 extracellular domain. P blocks HER2’s ability to heterodimerize with other HER/ErbB receptors. Methods: This Ph II trial evaluates the efficacy and safety of T with P in patients (pts) with HER2+ (FISH +) MBC who had progressive disease (PD) on T-based therapy. Eligible pts must have had = 3 T-based regimens, normal (nl) left ventricular ejection fraction (EF=55%) and without significant cardiac history. Pts received IV T (6mg/kg) and P (420 mg) every 3 weeks (wks). EKG plus echocardiogram (ECHO) or cardiac MRI and tumor response were assessed every 3 and 6 wks, respectively. Results: Eleven pts received 39 (1 to 13) cycles, 1 pt achieved a partial response (PR) and 3 pts had stable disease. A total of 68 ECHOs and 8 cardiac MRIs were performed. Left ventricular systolic dysfunction (LVSD) with nl EKG was seen in 5 pts; Grade (Gr) 1 (n = 2) (EF 50–55%), Gr 2 (n = 2) (EF 40–50%) and Gr 3 (n = 1) (EF20–40%). Gr 2–3 events were associated with global hypokinesis. Gr 3 event was associated with symptomatic CHF. All 5 pts had received 240mg/m2 cumulative dose of doxorubicin, 2 pts (Gr 2–3) received chest wall radiation, and 1 pt (Gr 1) had HTN. Two pts with Gr 1–2 LVSD had a history of reduced EF during prior T-based treatment, which reversed to nl upon stopping T. Reduced EF appeared within 1–2 cycles, which returned to nl in 3 pts within 1wk to 3 months (mo) post discontinuing T/P. One pt had persistent Gr 2 LVSD 3 mo after the initial event. The pt with Gr 3 LVSD had extensive chest wall disease and died of PD and possibly CHF 2 mo after treatment termination. Conclusions: We observed Gr 1–3 LVSD in patients with HER2+ MBC who received dual MoAB treatment directed at HER2, in which very strict cardiac surveillance guidelines were required. One of 11 pts achieved PR and 1 pt had symptomatic CHF thus far. It is unknown whether the other events would have become symptomatic if treatment had continued. Further evaluation of the efficacy of combination T with P is required to define the overall risk and benefit. No significant financial relationships to disclose.

Impedance Cardiography: A Comparison of Cardiac Output vs Waveform Analysis for Assessing Left Ventricular Systolic Dysfunction

Early detection of asymptomatic left ventricular systolic dysfunction (LVSD) is beneficial in managing heart failure. Recent studies have cast doubt on the usefulness of cardiac output as an indicator of LVSD. In impedance cardiography (ICG), the dZ/dt waveform has a systolic wave called the E wave. This study looked at measurements of the amplitude and area of the E wave compared with ICG-derived cardiac output, stroke volume, cardiac index, and stroke index as methods of assessing LVSD. ICG data were obtained from patients (n=26) admitted to a coronary care unit. Clinical LVSD severity was stratified into 4 groups (none, mild, moderate, and severe) based on echocardiography data and standard clinical assessment by a cardiologist blinded to ICG data. Statistical analysis showed that the E wave amplitude and area were better indicators of the level of LVSD than cardiac output, stroke volume, cardiac index, or stroke index. ICG waveform analysis has potential as a simple point-of-care test for detecting LVSD in asymptomatic patients at high risk for developing heart failure and for monitoring LVSD in patients being treated for heart failure.

Circumferential Versus Longitudinal Systolic Function in Patients with Hypertension: A Nonlinear Relation

Depressed circumferential midwall performance and impaired left ventricular (LV) longitudinal function are both early markers of LV systolic dysfunction in patients with hypertension. The relation between midwall and longitudinal indices in these patients has never been analyzed. In 126 patients with hypertension, midwall fractional shortening (mFS), stress-corrected mFS, M-mode left atrioventricular plane displacement, and tissue Doppler-derived peak mitral annular systolic velocity were determined. Regression analysis showed that the relations of midwall indices to atrioventricular plane displacement and mitral annular systolic velocity were all nonlinear. Reductions in atrioventricular plane displacement or mitral annular systolic velocity within their higher ranges corresponded to relatively smaller decreases in mFS and stress-corrected mFS. Relative wall thickness was the strongest determinant of the relative efficiency of circumferential and longitudinal LV contraction. The relation between circumferential midwall and longitudinal function in patients with hypertension is nonlinear and dependent on LV geometry. In these patients, systolic impairment occurs earlier in longitudinal than circumferential performance.

Quality of Life in Patients With Signs and Symptoms of Heart Failure—Does Systolic Function Matter?

The impaired quality of life in patients with systolic heart failure is well described. Less is known about patients with preserved systolic function (PSF) heart failure. We aimed to compare the quality of life in patients with PSF heart failure with that of those with left ventricular systolic dysfunction (LVSD) using generic and disease-specific quality-of-life questionnaires. Four hundred patients with signs and symptoms of heart failure referred for an echocardiogram to assess left ventricular function were invited to complete quality-of-life questionnaires. A total of 278 of 400 (69.5%) responses were adequate for analysis. The mean age of respondents was 72.5 (10) years; 132 (47%) were male. A total of 189 of 278 (68%) had PSF, and 89 of 278 (32%) had left ventricular systolic dysfunction (LVSD). Both groups were well matched for age, but there were more women in the PSF group (58% vs. 40%). No significant differences were found in the quality of life between PSF and LVSD patients. Women had significantly worse quality of life compared with men in both groups. Patients with PSF are an important subgroup of heart failure patients whose quality of life is as impaired as those with systolic dysfunction. These data suggest these patients warrant more care, perhaps in specialist clinics.

Heart failure and chronic obstructive pulmonary disease: An ignored combination?

To quantify the prevalence of heart failure and left ventricular systolic dysfunction (LVSD) in chronic obstructive pulmonary disease (COPD) patients and vice versa. Further, to discuss diagnostic and therapeutic implications of the co-existence of both syndromes. We performed a Medline search from 1966 to March 2005. The reported prevalence of LVSD among COPD patients varied considerably, with the highest prevalence (10-46%) among those with an exacerbation. One single study assessed the prevalence of heart failure in COPD patients. A prevalence of 21% of previously unknown heart failure was reported in patients with a history of COPD or asthma. We did not find any report on COPD in heart failure or LVSD patients. Diagnosing heart failure in COPD patients or vice versa is complicated by overlap in signs and symptoms, and diminished diagnostic value of additional investigations. In general, pulmonary and heart failure 'drug cocktails' can be administered safely to patients with concomitant COPD and heart failure, although (short acting) beta2-adrenoreceptor agonists and digitalis have potentially deleterious effects on cardiac and pulmonary function, respectively. Although knowledge about the prevalence of concomitant heart failure in COPD patients and vice versa is scarce, it seems that the combined presence is rather common. In view of diagnostic and therapeutic implications, more attention should be paid to the concomitant presence of both syndromes in clinical practice and research.

Diagnostic value of troponin T for alterations in left ventricular mass and function in dialysis patients

Cardiac troponin T (cTnT) is related to left ventricular (LV) mass in patients with end-stage renal disease (ESRD). Furthermore, cTnT reflects the severity of systolic dysfunction in patients with heart diseases. We tested the diagnostic value of cTnT for left ventricular hypertrophy (LVH) and LV systolic dysfunction in a large group of clinically stable hemodialysis patients without heart failure. CTnT was significantly (P < 0.001) higher in patients with LVH than in those with normal LV mass. In a multiple logistic regression model, adjusting for potential confounders (including cardiac ischemia), systolic pressure and cTnT (both P = 0.003) were the strongest correlates of LVH. Similarly, cTnT was significantly higher (P = 0.005) in patients with systolic dysfunction than in those with normal LV function and in a multiple logistic regression model cTnT ranked as the second independent correlate of this alteration after male sex. Serum cTnT had a high positive prediction value for the diagnosis of LVH (87%) but its negative prediction value was relatively low (44%). The positive predictive value of cTnT for LV dysfunction was low (25%) while its negative predictive value was high (93%). A combined analysis including systolic pressure (for the diagnosis of LVH) and sex (for the diagnosis of LV systolic dysfunction) augmented the diagnostic estimates to an important extent (95% positive prediction value for LVH and 98% negative prediction value for LV systolic dysfunction). CTnT has a fairly good diagnostic potential for the identification of LVH and for the exclusion of LV systolic dysfunction in patients with ESRD without heart failure. This marker may be useful for the screening of alterations in LV mass and function in clinically stable hemodialysis patients.

Accuracy of estimating exercise prescription intensity in patients with left ventricular systolic dysfunction.

Exercise prescription in patients with left ventricular systolic dysfunction (LVSD) is difficult. Exercising beyond ventilatory threshold (VT) can have negative physiologic effects; therefore, exercise prescribed above VT may be detrimental. A majority of cardiac rehabilitation programs use the Karvonen/heart rate reserve (HRR) method, rating of perceived exertion (RPE), and/or a percentage of oxygen consumption to prescribe exercise intensity. The purpose of this study was to determine if these methods correlate with an exercise intensity below VT in LVSD patients. The authors studied 52 patients (37 males, 15 females; age 52 +/- 13 years; left ventricular ejection fraction 27% +/- 8%) who underwent a symptom-limited cardiopulmonary exercise test and reached VT to determine functional capacity and exercise prescription. Peak heart rate (HR) as well as HRR derived minimum (60%), midpoint (70%), and maximum (80%) HR were highly correlated (P < 0.001) with HR at VT. Using these three different HR cutoff formulas from HRR, 15% to 62% of patients were prescribed exercise outside the range of VT-HR +/- 10%. The midpoint (70% HRR) best predicted exercise HR in the VT-HR +/- 10% range (73% of patients). Mean oxygen consumption at VT was 83 +/- 9% of peak oxygen consumption. There was no correlation (P < 0.16) between RPE and VT. The Karvonen/HRR method failed to estimate HR-VT +/- 10% in a large percentage of patients with LVSD. There was no correlation between RPE and VT. Based on these data, exercise training intensity should ideally be prescribed based on the HR identified at VT using cardiopulmonary exercise testing in patients with LVSD.

Case Finding for Computerized Clinical Reminders: To Whom do the Guidelines Apply?

PURPOSE: An often overlooked problem with clinical guideline implementation is the identification of patients to whom the guidelines should be applied. This study developed and validated a computerized tool to identify patients with congestive heart failure (CHF) who would be candidates for management according to a computerized version of a clinical practice guideline. METHODS: A retrospective cohort study was conducted in the General Internal Medicine Clinic at the VA Puget Sound Health Care System. Subjects having at least one echocardiogram (Echo) or radionuclide ventriculogram during 1996–1998 were included. CHF was defined by left ventricular systolic dysfunction (LVSD) on either study. Subjects were randomly split into two samples; one for prediction model development and the second for validation. To determine the utility of clinical data in discriminating between patients with and without CHF, we examined demographic variables, pharmacy data, and inpatient and outpatient primary or secondary ICD-9 codes (428,398.91) that were available from VA administrative database. The medications of interest included ACE inhibitors, AII antagonists, beta-blockers, calcium channel blockers, digoxin, diuretics, and nitrates. Discriminant analysis was used to build predictive models to identify LVSD patients using pharmacy and demographic data. Accuracy of both the prediction model and diagnosis was compared to presence of LVSD as determined by cardiac imaging. RESULTS: 1314 subjects had at least one cardiac imaging study. 536 (40.8%) met criteria for LVSD. The mean age was 68, 84% were Caucasian, and 97% males. Subjects with LVSD were slightly older than those without LVSD (69 versus 67, p = 0.004), but were similar with regard to gender, race and marital status. Subjects with LVSD were more likely to have prescriptions for ACE inhibitors, aspirin, digoxin, loop diuretics, hydralazine and nitrates. (Carvedilol was not on formulary during the study period.) ACE inhibitors, aspirin, digoxin, loop diuretics, hydralazine, nitrates and age were included in the final predictive model. Use of ACE inhibitors, loop diuretics and digoxin exerted the greatest predictive power. The predictive model was 70% accurate (72% sensitivity, 69% specificity), while ICD-9 codes were 72% accurate (74% sensitivity, 71% specificity). CONCLUSION: A model using pharmacy data identified most subjects with CHF, and performed equally well compared to ICD-9 codes in the VA database. Although the model did not demonstrate improvement over ICD-9 codes, it was able to predict LVSD using a relatively small number of potential covariates.