Performance et rendement du ventricule gauche chez l’hypertendu sans hypertrophie ventriculaire gauche : étude échographique par modélisation du couplage ventriculo-aortique

Because the functional interaction between the LV and arterial systems, termed ventricular-arterial coupling, is recognized as a key determinant of LV performance, the objective of the present study was to assess the impact of uncomplicated HT without LVH on LV performance using simultaneously echocardiography and carotid tonometry. LV maximal power (PmaxVG), cardiac power output (CPO), LV efficiency (CPO/PmaxVG), input aortic and output LV elastance (Ea and Ees) were assessed in 20 normotensive control subjects (NT) and 10 patients with untreated HT. PmaxVG was calculated according to the integral of the product of LV wall stress with strain rate (as an index of gradient velocity). Cyclic variation of wall thickness and SR were measured by speckel-tracking. Ea and Ees were derived and modelized from the pressure–volume curve. No difference in age, BMI and sex ratio was observed between NT and HT. Systolic BP (160 ± 18 vs. 119 ± 10 mmHg), LV mass (99 ± 15 vs. 76 ± 12 g/m²), PWV (9.7 ± 2 vs. 6.9 ± 1 m/s) were significantly higher (P < 0.01) in HT when compared to NT. In HT increased of CPO and Ea was compensated by an increase of LV (15 ± 4 vs. 12 ± 3%, P < 0.02) and Ees (5.5 ± 2 vs. 4.5 ± 1.5 mmHg/mL), which are significantly elevated in HT (P < 0.05). No difference was observed in Ea/Ees between NT and HT. In conclusion at the early phase of HT, in patients without LVH, LV performance and ventricular-arterial coupling were adapted to post-load elevation. This adaptation may be the result of an increased of LV contractility.     

Early and late cardiac ventricular reverse remodeling after catheter ablation for lone paroxysmal atrial fibrillation

Aim

We sought to explore ventricular function in patients with lone paroxysmal atrial fibrillation (AF) and determine the mid- and long-term impact of pulmonary vein isolation on cardiac remodeling.

Background

The relationship between tachyarrhythmia and ventricular dysfunction is still a matter of debate. Tachycardia-induced cardiomyopathy is defined as reversible myocardial dysfunction following treatment for tachyarrhythmia.

Method

We prospectively studied 31 patients (56.4 ± 10 years) presenting with paroxysmal-AF who were treated successfully by catheter ablation and 15 age-matched controls. Left and right ventricular functions were assessed by echocardiography at baseline and at 3-month and 1-year follow-up.

Results

In AF-patients, LV-function was slightly lower at baseline than controls (LV-ejection fraction was 60% versus 64%; P = 0.06). More impressive, systolic peak velocity on Doppler tissue imaging was 9 cm/s in AF patients (versus 12 cm/s; P = 0.0004). LV global longitudinal strain was also significantly different between the two groups (patients: −16% versus controls: −19%; P = 0.005). At 1-year follow-up, most functional parameters significantly improved in the AF-patients and no longer differed from the controls. Right ventricular (RV) function was also depressed in AF patients at baseline. At 1-year follow-up, tissue Doppler showed improvement in RV-S′ (+27%, P = 0.007) and RV peak systolic strain (+36%, P < 0.0001) and became comparable to controls.

Conclusion

We demonstrate that some degree of arrhythmic cardiomyopathy exists in patients presenting with lone paroxysmal-AF. Catheter ablation improved RV and LV functions. Longitudinal function is the most sensitive component of ventricular systole to monitor when looking for this cardiac reverse remodeling.     

Body temperature circadian rhythm variability corresponds to left ventricular systolic dysfunction in decompensated cardiomyopathic hamsters

Background

A declining amplitude of body temperature circadian rhythm (BTCR) predicts decompensation or death in cardiomyopathic hamsters. We tested the hypothesis that changes in BTCR amplitude accompany significant changes in left ventricular (LV) size and function.

Methods and Results

Using intraperitoneal transmitters, we continuously monitored the temperature of 30 male BIO TO-2 Syrian dilated cardiomyopathic hamsters. Cosinor analysis was used to detect significant changes—defined as changes >1 standard deviation from the baseline amplitude for 3 consecutive days—in BTCR amplitude over each hamster’s lifespan. The Student t-test was used to compare BTCR variability and LV size and function (as assessed by 2D echocardiography) between baseline and the time that BTCR amplitude declined. All hamsters received 10 mg/kg furosemide daily. At the time of BTCR amplitude decline, functional parameters had changed significantly (P < .0001) from baseline: ejection fraction (0.31 ± 0.09% vs. 0.52 ± 0.08%), LV end-systolic volume (0.11 ± 0.03 vs. 0.05 ± 0.02 cm³), and LV end-diastolic volume (0.16 ± 0.04 vs. 0.10 ± 0.03 cm³).

Conclusions

In decompensated cardiomyopathic hamsters, a decline in BTCR amplitude was associated with progression of heart failure and cardiac decompensation. Variation in BTCR warrants further investigation because of its potential implications for the diagnosis and treatment of cardiovascular disorders.     

Dual Site Right Atrial Pacing can Improve the Impact of Standard Dual Chamber Pacing on Atrial and Ventricular Mechanical Function in Patients with Symptomatic Atrial Fibrillation: Further Observations from the Dual Site Atrial Pacing for Prevention of Atrial Fibrillation Trial

Background: The effects of atrial pacing mode on atrial and ventricular function in patients with atrial fibrillation (AF) and bradycardia have not been evaluated. We evaluated atrial and ventricular function during randomization to support pacing (SP), high right atrial pacing (HRA), and dual site right atrial pacing (DAP).Methods: Seventy-nine patients (66 ± 12 yr, 46 male) with standard pacing indications and symptomatic AF were randomized to each of three pacing modes (DAP, HRA, SP) for 6 months in a crossover design. Echocardiographic studies were performed at enrollment and the end of each mode. Paired comparisons of atrial and ventricular function parameters were performed between each pacing mode and baseline.Results: HRA pacing in DDDR mode resulted in increased left ventricular (LV) end systolic volume (78 ± 42 vs. 60 ± 31 ml, p = 0.001) and reduced LV ejection fraction (44 ± 14 vs. 50 ± 11%, p = 0.007) compared to baseline. These parameters did not change during DAP. DAP resulted in increased peak A wave velocity (75 ± 19 vs. 63 ± 23 cm/s, p = 0.003) and atrial filling fraction compared to baseline (0.47 ± 0.15 vs. 0.38 ± 0.13, p = 0.005). Atrial and ventricular function were similar between control and SP.Conclusion: DAP, but not HRA or SP, improved left atrial (LA) function in patients with AF and bradycardia. HRA pacing in DDDR mode resulted in LA dilatation and deterioration of LV function which was not observed with DAP.This study was supported by a grant from the Electrophysiology Research Foundation, Warren, NJ and Medtronic Inc., Minneapolis, MN. Drs. Delfaut and Prakash were supported by grants from the Electrophysiology Research Foundation during the term of this study. Drs. Saksena and Nanda were consultants to Medtronic during this study. Dr. Hettrick and Mr. Ziegler are employees of Medtronic.     

Acute and Chronic Effects of Cryoablation of the Pulmonary Veins in the Dog as a Potential Treatment for Focal Atrial Fibrillation

Background: Atrial fibrillation (AF) may be triggered by premature atrial depolarizations originating in the pulmonary veins (PV). Radiofrequency catheter ablation of PV foci may prevent recurrence of AF, but may cause PV stenosis. Therefore, a safer method for ablation of PV foci is needed. This study evaluated the acute and chronic effects of PV ablation using a cryocatheter ablation (CCA) system, which may be less likely to cause PV stenosis. Methods: CCA was performed by freezing for 5 minutes or more in one or more PVs in 10 anesthetized dogs. Pacing threshold and vessel diameter were measured before and after PV cryoablation. All dogs were restudied at 4.0 ± 1.64 months (range 2–7) in a manner identical to baseline. Results: CCA was performed in 27 PVs (range 1–4/dog), with a mean freeze time of 8.62 ± 5.42 minutes per vein (range 5.23–22.06). Mean temperature for all freezes was –65 ± 5.3°C. Mean PV diameter was 6.49 ± 1.73 vs 6.24 ± 1.83 mm (p = NS) and mean pacing threshold 1.32 ± 0.75 vs 9.36 ± 5.93 mA (p < .01), before vs. acutely after ablation. At followup, at the ablation sites PV diameter (7.02 ± 1.88 mm) was unchanged from baseline, whereas pacing threshold remained elevated (2.54 ± 1.44 mA, p < .05 vs baseline). There were no acute or long-term complications. Conclusions: (1) CCA of PVs produced a significant rise in acute and chronic pacing threshold indicating loss of atrial conductivity. (2) CCA of PVs did not cause PV stenosis or other complications. (3) The data suggest that CCA of PVs may be a safe and effective method for treating focal AF.     

Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation

Aims Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post–repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium. Methods In 12 patients with persistent AF (11 male, 58 ± 5 yrs, 27 ± 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined. Results Both drugs prolonged APD90 during AF (flecainide from 109 ± 7 ms to 137 ± 10 ms, sotalol from 108 ± 6 ms to 131 ± 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 ± 8 ms to 139 ± 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 ± 9 ms to 197 ± 28 ms, p < 0.05 vs. baseline and vs. sotalol). Conclusions Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.Drs. Kirchhof, Engelen and Breithardt are Members of the Kompetenznetz Vorhofflimmern     

Right Ventricular Pacing With Mechanical Dyssynchrony Causes Apoptosis Interruptus and Calcium Mishandling

Background

Mechanical dyssynchrony associated with rapid pacing induces cardiac cell stress and myocardial apoptotic pathway activation that has been implicated in the pathophysiology of left ventricular (LV) dysfunction. Effects of dyssynchrony per se are not fully understood. The objective of our study was to test whether ventricular dyssynchrony would elicit myocardial alterations in LV calcium handling regulation and cell survival or apoptosis signalling in right ventricular-paced swine.

Methods

Implantation of pacemaker was performed under anaesthesia. Endocardial bipolar screw lead was inserted into the right jugular vein and positioned either in the right atrium or at the right ventricular (RV) apex. Swine were paced at 150 beats per minute for 3 weeks.

Results

Compared with right atrial pacing, RV pacing led to abnormal LV sarcoplasmic reticulum calcium uptake (315 ± 65 vs 155 ± 55 nmol/min/mg, P < 0.05) and LV calcium-handling protein expression, ie, 35% reduction in ryanodine receptor 2, 25% decline in sarcoplasmic reticulum Ca²⁺ ATPase, 70% increase in Na⁺/Ca²⁺ exchanger, and 10% increase in phospholamban. RV pacing also elicited activation of LV apoptotic cascades without nuclear apoptosis. So-called interrupted apoptosis was the result of increased expression of X-linked inhibitor of apoptosis protein. Apoptosis and calcium mishandling were documented in absence of depressed heart function (ejection fraction 62 ± 8% vs 57 ± 12%, in right atrial- and RV-paced hearts, respectively, P > 0.05).

Conclusions

Slow rate RV pacing causes mechanical dyssynchrony and profound LV alterations in both apoptotic pathways and calcium handling in the early stages of pacing-induced cardiomyopathy.     

Left ventricular and myocyte structure and function following chronic ventricular tachycardia in rabbits

Summary Recent studies have shown that chronic pacing induced tachycardia in large animals such as dogs and pigs causes congestive heart failure accompanied by myocyte contractile abnormalities, neurohormonal activation, alterations in sarcolemmal receptor systems, and changes in myocardial structure. However, fundamental studies directed at identifying basic contributory mechanisms responsible for the development of this form of heart failure are problematic in these large animals. Accordingly, the present study examined the direct effects of pacing induced tachycardia upon LV and myocyte structure and function in the adult rabbit. Twelve adult rabbits (New Zealand White; 3.5–4.5 Kg) underwent 30 days of pacing induced ventricular tachycardia (VT; right ventricular paced, 400 bpm) and 12 additional age and weight matched rabbits served as controls. Echocardiography revealed increased LV end-diastolic dimension (1.92±0.04 vs 1.10±0.20 cm;p<0.05) and decreased fractional shortening (41.5±3 vas 22.3±4%;p<0.05) in the VT group compared to controls with no change in LV mass. Steadystate isolated myocyte contractile function was significantly reduced in the VT group compared to control. For example, isolated myocyte velocity of shortening was 41±2 m/s in the VT group compared to 84±5 m/s for controls (p<0.05). In the presence of 8 mM extracellular Ca²⁺, myocyte velocity of shortening was 40% lower in the VT group compared to controls. Finally, myocyte contractile responsiveness with -adrenergic receptor stimulation was reduced by 52% in the VT group compared to controls. Isolated myocyte length significantly increased in the VT group compared to control (157±3 vs 128±2 m;p<0.05) with a concomitant decrease in cross-sectional area (274±6 vs 400±31 m²;p<0.05). Myocyte myofibril volume fell by 27% in the VT group compared to control with no change in mitochondrial percent volume. In summary, this study demonstrated that chronic pacing induced tachycardia in rabbits caused: 1) LV dilation and dysfunction, 2) depressed isolated myocyte contractile function and inotropic responsiveness, and 3) alterations in myocyte structure and composition. The changes in LV and myocyte function and structure following chronic tachycardia in rabbits are similar to that reported previously with tachycardia induced heart failure in larger animals. These findings suggest that this rabbit model of chronic tachycardia may provide a useful and practical means by which to examine basic mechanisms responsible for the development of congestive heart failure.Supported by National Institutes of Health Grant HL45024. Dr. Spinale is an Established Investigator of the American Heart Association     

Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation

Atrial dilatation is an independent risk factor for thromboembolism in patients with and without atrial fibrillation (AF). In many patients, atrial dilatation goes along with depressed contractile function of the dilated atria. While some mechanisms causing atrial contractile dysfunction in fibrillating atria have been addressed previously, the cellular and molecular mechanisms of atrial contractile remodeling in dilated atria are unknown. This study characterized in vivo atrial contractile function in a goat model of atrial dilatation and compared it to a goat model of AF. Differences in the underlying mechanisms were elucidated by studying contractile function, electrophysiology and sarcoplasmic reticulum (SR) Ca²⁺ load in atrial muscle bundles and by analyzing expression and phosphorylation levels of key Ca²⁺-handling proteins, myofilaments and the expression and activity of their upstream regulators. In 7 chronically instrumented, awake goats atrial contractile dysfunction was monitored during 3 weeks of progressive atrial dilatation after AV-node ablation (AV block goats (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC), transmembrane action potentials (APs) and rapid cooling contractures (RCC, a measure of SR Ca²⁺ load) were studied in right atrial muscle bundles. Total and phosphorylated Ca²⁺-handling and myofilament protein levels were quantified by Western blot. In AVB goats, atrial size increased by 18% (from 26.6 ± 4.4 to 31.6 ± 5.5 mm, n = 7 p < 0.01) while atrial fractional shortening (AFS) decreased (from 18.4 ± 1.7 to 12.8 ± 4.0% at 400 ms, n = 7, p < 0.01). In open chest experiments, AWI was reduced in AVB and in AF goats compared to controls (at 400 ms: 8.4 ±0.9, n = 7, and 3.2 ± 1.8, n = 5, vs 18.9 ± 5.3 mm×mmHg, n = 7, respectively, p < 0.05 vs control). FC of isolated right atrial muscle bundles was reduced in AVB (n = 8) and in AF (n = 5) goats compared to controls (n = 9) (at 2 Hz: 2.3 ± 0.5 and 0.7 ± 0.2 vs 5.5 ± 1.0 mN/mm², respectively, p < 0.05). APs were shorter in AF, but unchanged in AVB goats. RCCs were reduced in AVB and AF versus control (AVB, 3.4 ± 0.5 and AF, 4.1 ± 1.4 vs 12.2 ± 3.2 mN/mm², p < 0.05). Protein levels of protein kinase A (PKA) phosphorylated phospholamban (PLB) were reduced in AVB (n = 8) and AF (n = 8) vs control (n = 7) by 37.9 ± 12.4% and 29.7 ± 10.1%, respectively (p < 0.01), whereas calmodulin-dependent protein kinase II (CaMKII) phosphorylated ryanodine channels (RyR2) were increased by 166 ± 55% in AVB (n = 8) and by 146 ± 56% in AF (n = 8) goats (p < 0.01). PKA-phosphorylated myosin-binding protein-C and troponin-I were reduced exclusively in AVB goat atria (by 75 ± 10% and 55 ± 15%, respectively, n = 8, p < 0.05). Atrial dilatation developing during slow ventricular rhythm after complete AV block as well as AF-induced remodeling are associated with atrial contractile dysfunction. Both AVB and AF goat atria show decreased SR Ca²⁺ load, likely caused by PLB dephosphorylation and RYR2 hyperphosphorylation. While shorter APs further compromise contractility in AF goat atria, reduced myofilament phosphorylation may impair contractility in AVB goat atria. Thus, atrial hypocontractility appears to have distinct molecular contributors in different types of atrial remodeling.     

The cardiac component of cardiac cachexia

Background Recent evidence suggests the importance of noncardiac mechanisms in the genesis of the syndrome of cardiac cachexia. This raises the question of the relative role of the heart itself in this syndrome. This study sought to assess the cardiac dimensions, mass, and function and changes in these parameters over time in patients with chronic heart failure with and without cachexia. Methods Doppler echocardiography was performed in 28 patients with nonedematous weight loss (>7.5% over a period of >6 months) compared with 56 matched patients without weight loss in a ratio of 1:2 (age 71 ± 13 vs 67 ± 8 years, P = .07; New York Heart Association class 2.9 ± 0.7 vs 2.6 ± 0.6, P = .08). In 18 cachectic and 35 noncachectic patients with previous echocardiographic recordings, we analyzed the changes in left ventricular (LV) dimensions and mass over time. Results Cardiac dimensions including LV diastolic (69 ± 9 mm vs 67 ± 13 mm) and systolic cavity diameter (58 ± 11 mm vs 55 ± 15 mm), LV mass (480 ± 180 g vs 495 ± 190 g), and LV systolic and diastolic function including fractional shortening (16% ± 10% vs 18% ± 10%), isovolumic relaxation time (29 ± 22 ms vs 36 ± 27 ms), and E/A ratio (2.7 ± 1.6 vs 3.3 ± 2.9) did not differ between cachectic and noncachectic patients (all P > .1). By analyzing changes in LV mass over time, we found an increase (>20%) in 2 (11%) cachectic and 14 (40%) noncachectic patients and a decrease in LV mass (>20%) in 9 (50%) cachectic and 8 (23%) noncachectic patients (χ² test, P < .05). Conclusions Although no specific cardiac abnormality could be detected echocardiographically in cachectic patients compared with patients with noncachectic chronic heart failure in a cross-sectional study, over time a significant loss of LV mass (>20%) occurs more frequently in patients with cardiac cachexia. (Am Heart J 2002;144:45-50.)     

Mechanical Synchrony: Role of Surgical Ventricular Restoration in Correcting LV Dyssynchrony During Chamber Rebuilding

Cardiac failure is frequently complicated by intra and or interventricular conduction delay that results in dyssynchronized cardiac contraction and relaxation. In contrast to an electrical intervention by biventricular pacing, this study tests the capacity of geometric rebuilding by surgical ventricular restoration (SVR) to restore a more synchronous contractile pattern through mechanical reconstruction without exogenous pacing input.Thirty patients (58 ± 8 years) undergoing SVR at the Cardiothoracic Center of Monaco were prospectively evaluated with a protocol which uses simultaneous measurements of ventricular volumes and pressure to construct pressure/volume (P/V) and pressure/length (P/L) loops. Mean QRS duration was within normal limits (100± 17 ms) preoperatively. Preoperative LV contraction was highly asynchronous. Endocardial time motion was either early or delayed at the end-systolic phase, yielding P/L loops with abnormal in size, shape, and orientation. Postoperatively, SVR resulted in leftward shifting of P/V loops and increased area; endocardial time motion and P/L loops almost normalized. The hemodynamic consequences of SVR included improved ejection fraction; reduced end-diastolic and end-systolic volume index; more rapid peak filling rate; peak ejection rate and mechanical efficiency resulting in mechanical intraventricular resynchronization that improves LV performance.     

Right ventricular pacing can induce ventricular dyssynchrony in patients with atrial fibrillation after atrioventricular node ablation.

OBJECTIVES: This study was designed to assess the effects of long-term right ventricular (RV) pacing on left ventricular (LV) dyssynchrony, LV function, and heart failure symptoms. BACKGROUND: Atrioventricular (AV) node ablation and subsequent long-term RV pacing is a well-established treatment option in patients with atrial fibrillation (AF). METHODS: In 55 patients with drug-refractory AF, AV node ablation and implantation of a pacemaker was performed. At baseline and after a mean of 3.8 +/- 1.7 years, LV dyssynchrony (by M-mode echocardiography and tissue Doppler imaging), LV function, and volumes and functional status were assessed. RESULTS: After long-term RV pacing, 27 patients (49%) had developed LV dyssynchrony. Concomitantly, these patients worsened in heart failure symptoms (New York Heart Association functional class increased from 1.8 +/- 0.6 to 2.2 +/- 0.7, p < 0.05), with a decrease in LV ejection fraction (from 48 +/- 7% to 43 +/- 7%, p < 0.05) and an increase in LV end-diastolic volume (from 116 +/- 39 ml to 130 +/- 52 ml, p < 0.05). Conversely, patients without LV dyssynchrony did not deteriorate in heart failure symptoms, LV function, or LV volumes. CONCLUSIONS: Long-term RV pacing can induce LV dyssynchrony in almost 50% of patients treated with AV node ablation for chronic AF. The development of LV dyssynchrony was associated with deterioration in heart failure symptoms, systolic LV function, and LV dilatation.     

Pacemaker-Detected Atrial Fibrillation in Patients With Pacemakers: Prevalence,Predictors, and Current Use of Oral Anticoagulation

Background

Dual-chamber pacemakers frequently document atrial fibrillation (AF) in patients without symptoms. Pacemaker-detected AF is associated with a 2.5-fold increased risk of stroke, although it is not established whether oral anticoagulation reduces this risk. This study sought to determine the prevalence and predictors of pacemaker-detected AF and to document current oral anticoagulant use.

Methods

A retrospective analysis included all patients from a single academic hospital who had pacemakers capable of documenting AF. Blinded evaluation of all echocardiograms conducted within 6 months of implantation was performed.

Results

Of 445 patients, pacemaker-detected AF was present in 246 (55.3%), who were older (74.3 ± 13.7 years vs 71.7 ± 14.4, P = 0.046), more likely to have a history of clinical AF (29.7% vs 19.1%, P = 0.01), and had a larger left atrial volume index (34.4 ± 11.8 mL/m² vs 30.0 ± 9.9 mL/m², P = 0.019) than the patients without pacemaker-detected AF. Among patients without a clinical history of AF, left atrial volume index was higher among those with pacemaker-detected AF (33.7 ± 11.3 mL/m² vs 29.0 ± 10.1 mL/m², P = 0.034). Anticoagulants were used in 35.3% of patients with pacemaker-detected AF, compared with 21.6% of patients without (P < 0.05). In patients with pacemaker-detected AF, anticoagulants were used more frequently among patients who also had clinical AF (58.9%) compared with those without (23.7%, P < 0.001).

Conclusions

Pacemaker-detected AF occurs in 50% of pacemaker patients and is treated with anticoagulants in less than 25% of patients who do not have a history of clinical AF. Clinical trials are needed to determine the role of anticoagulation in this population.     

Relationship of ventricular longitudinal function to contractile reserve in patients with mitral regurgitation

Background

Latent left ventricular (LV) dysfunction in patients with valvular or myocardial disease may be identified by loss of contractile reserve (CR) at exercise echocardiography. Contraction in the LV longitudinal axis may be more sensitive than radial contraction to minor disturbances of LV function. We sought to determine whether tissue Doppler measurement of longitudinal function could be used to identify CR.

Methods

Exercise echocardiography was performed in 86 patients (20 women, age 53 ± 18 years), 72 with asymptomatic or minimally symptomatic mitral regurgitation, and 14 normal controls. Pulsed-wave tissue Doppler imaging (DTI) was used to measure maximum annular systolic velocity at rest and stress. Inducible ischemia was excluded by analysis of wall motion by an experienced observer. CR was defined by ≥5% improvement of stress compared with rest ejection fraction (EF). Exercise capacity was assessed from expired gas analysis.

Results

CR was present in 34 patients with mitral regurgitation (47%); peak EF in patients with and without CR was 74% ± 11% versus 54% ± 15% (P < .0001). CR could not be predicted by resting EF, volumes or sphericity, and DTI measurement of base-apex function was the only resting echocardiographic parameter to distinguish between patients with and without CR (10 ± 2 vs 8 ± 2 cm/s, P < .03). This parameter showed greater differences after stress (14 ± 4 vs 11 ± 3 cm/s, P < .001). Patients with CR showed lower peak DTI than controls, as well as lower exercise capacity and EF response to exercise. In a multiple linear regression model, rest DTI (P = .03) was an independent correlate of contractile reserve. The other correlates were age (P < .0001), resting (P < .0001) and peak end-systolic volume (P = .01), and resting (P < .0001) and peak end-diastolic volume (P < .0001); the model r² was 0.93 (P < .001).

Conclusion

In the absence of regional LV dysfunction, measurement of longitudinal axis function by DTI may be a marker of CR.     

Associations of big endothelin-1 and C-reactive protein in atrial fibrillation

Background Atrial fibrillation (AF) is associated with inflammation and endothelial dysfunction. However, the association between inflammation (as indexed by high-sensitivity C-reactive protein, hs-CRP) and endothelial function [as indexed by big endothelin-1 (ET-1)] in AF patients remains unclear. Methods We enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups. Results Patients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF (P < 0.05), both groups had higher hs-CRP level than controls (P < 0.05). Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance (P > 0.05), and both groups had higher big ET-1 levels than controls (P < 0.05). Multiple regression analyses revealed hs-CRP as an independent determinant of AF (P < 0.001). Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF (P < 0.001), but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients (r = 0.563, P < 0.05), however, the relationship in persistent AF patients was poor (r = 0.094, P < 0.05). Conclusions Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET-1 level.     

Aortic root dysfunctioning and its effect on left ventricular function in Ross procedure patients assessed with magnetic resonance imaging

Background

This study evaluated the diameters and distensibility of the aortic root as well as the degree of aortic regurgitation (AR) and its effect on left ventricular (LV) function in patients 8.2 ± 3.1 years after they underwent the Ross procedure, with a comparison of these parameters between patients and matched healthy subjects.

Methods

Eighteen Ross procedure patients (16 male patients, age [mean ± SD] 19.2 ± 3.8 years) and 18 matched healthy subjects (16 male patients, age [mean ± SD] 19.7 ± 4.2 years) underwent magnetic resonance imaging. Measurements for diameters (at 4 levels) and the distensibility of the aortic root were performed using a steady-state free precession sequence. Aortic flow was assessed with a velocity-encoded phase-contrast sequence. Left ventricular systolic function was assessed with a gradient-echo sequence in the short-axis plane. Comparison of parameters was performed using the Mann-Whitney U test. Correlations between diameters, distensibility, AR fraction, and LV systolic function were expressed with Spearman rank correlation coefficients. Linear regression analysis was used to identify predictors of LV systolic dysfunction.

Results

Aortic root diameters were increased in Ross procedure patients as compared with healthy subjects (mean difference 6.3-11.6 mm, P ≤ .02 at all 4 levels). Distensibility of the aortic root was lower in patients (1.9 ± 1.1 vs 7.8 ± 3.3 mm Hg⁻¹, P < .01). An AR fraction >5% was present in 14 of the 18 patients (mean AR fraction 8% ± 5% vs 1% ± 1%, P < .01). Left ventricular ejection fraction was lower in patients (50% ± 6% vs 57% ± 6%, P < .01). Dilatation, decreased distensibility, and AR fraction were correlated with impaired LV systolic function (P < .05 for all). The AR fraction predicted impaired LV systolic function (P < .01).

Conclusions

Magnetic resonance imaging shows dilatation and decreased distensibility of the aortic root, AR, and consequent impaired LV systolic function in patients after the Ross procedure.     

Acute Effects of Withdrawal of Cardiac Resynchronization Therapy on Left and Right Ventricular Function,Dyssynchrony, and Contractile Function in Patients With New York Heart Association Functional Class I/II Heart Failure: MADIT-CRT

BackgroundCardiac resynchronization therapy (CRT) improves left ventricular (LV) function, size, mitral regurgitation, and clinical outcomes. Whether these improvements are due to the short-term effects of improvement in synchrony or contractile performance, or to long-term improvement in ventricular structure and function remains insufficiently elucidated.Methods and ResultsWe used echocardiographic data from 63 patients enrolled in the MADIT-CRT trial who, after 1 year of CRT therapy, underwent echocardiographic evaluation with CRT turned both on and off within minutes. LV volumes, LV ejection fraction, left atrial (LA) volumes, and right ventricular function were assessed at baseline and in the on and off modes within a 5-minute time-frame at 12 months. Speckle-tracking strain analysis was used to assess LV dyssynchrony and contractile function. Interruption of long-term CRT resulted in acute deterioration of LV and RV function and acute increase in LV and LA volumes, although not to baseline. Acute withdrawal was also associated with increased dyssynchrony (SD time to peak transverse strain 178 ± 68 ms vs 195 ± 62 ms; P = .16; and SD time to peak longitudinal strain 108 ± 46 ms vs 125 ± 55 ms; P = .046). However, there was no deterioration in contractile function (global longitudinal strain), which had improved with CRT (?9.8 ± 4.3% vs ?10.0 ± 3.7%; P = .93).ConclusionsDespite substantial LV reverse remodeling with CRT, interruption of long-term CRT after 12 months resulted in an acute worsening of LV size and function, LA volumes, and right ventricular function, with concomitant worsening of ventricular synchrony despite minimal change to the observed improvement in LV strain measures of contractile function. These findings suggest that the beneficial reverse remodeling associated with CRT may be mostly dependent on active pacing, although intrinsic improvements in contractile function may persist beyond termination of pacing.     

Inhibition of NOS2 ameliorates cardiac remodeling,improves heart function after myocardial infarction in rats

Abstract. Objective: Previous studies have shown increased expression of nitric oxide synthase 2 (NOS2) in rat heart several weeks after myocardial infarction (MI). The aim of this study was to examine the effect of chronic administration of S-methylisothurea (SMT), a selective NOS2 inhibitor, commenced one week after MI on hemodynamic parameters and left ventricular (LV) remodeling in rats. Methods: Rats with MI induced by left coronary ligation were given SMT (0.5 mg/kg/d) or saline by gavage starting one week after MI. After chronic administration for five weeks, hemodynamic and cardiac morphologic studies were performed, and lung water content, plasma NO_x concentration, NOS2 protein level, myocyte size and collagen volume fraction of noninfarct LV area were quantified. Results: The NO_x concentration in plasma and the NOS2 protein level in noninfarct myocardium in MI rats were higher than controls. When compared with the MI rats receiving saline, chronic administration of SMT reduced myocyte size (15.1 ± 1.6 µm vs 16.9 ± 2.3 µm, P < 0.05), collagen volume fraction of noninfarct LV area (4.4% ± 1.1% vs 5.7% ± 1.2%, P < 0.01) and lung water content (77.4% ± 1.4% vs 79.3% ± 0.9%, P < 0.01), without affecting infarct size. Administration of SMT had no significant effect on heart rate and mean arterial pressure, but decreased LV end-diastolic pressure (8.7 ± 2.1 mmHg vs 13.4 ± 3.1 mmHg, P < 0.01), central venous pressure (0.9 ± 0.3 mmHg vs 1.5 ± 0.5 mmHg, P < 0.01) and inner LV diameter (6.9 ± 0.3 mm vs 7.2 ± 0.3 mm, P < 0.05) in the MI rats. Plasma level of NO_x in the MI rats receiving SMT was reduced to control level. Conclusions: Chronic administration of SMT had beneficial effects on LV remodeling and cardiac dysfunction in MI rats, suggesting the possibility that inhibition of NOS2 could be a therapeutic tool for cardiac dysfunction after MI.     

Catheter ablation for atrial fibrillation in patients with left ventricular systolic dysfunction. A systematic review and meta-analysis

Background

Atrial fibrillation (AF) and heart failure are often coexisting major public health burdens. Although several studies have reported partial restoration of systolic left ventricular (LV) function after catheter ablation for AF, the method is not widely applied in patients with LV dysfunction. We reviewed the results of AF ablation in patients with systolic LV dysfunction.

Methods and Results

PubMed was searched for studies published after 2000 reporting original data on AF catheter ablation in adult patients with systolic LV dysfunction. Primary end point was the change of LV ejection fraction (LVEF) after catheter ablation; secondary endpoints were the changes of exercise capacity and quality of life after the procedure. We calculated mean difference (MD) of LVEF and 95% confidence interval (95% CI) using random-effects models. Heterogeneity was investigated by I² statistic, publication bias with Egger's test. The impact of covariates on LVEF improvement was evaluated with meta-regression analyses. Nine studies with a total of 354 patients with systolic LV dysfunction were analyzed. Study patients were mainly male with mean age 49 to 62 years, LVEF was moderately impaired and ranged in all but 1 study from 35% to 43%. LVEF improved after ablation with a MD of 11.1% (95% CI: 7.1–15.2, P < .001). Heterogeneity among analyzed studies was significant (I² = 92.9, P < .001). No potential publication bias was found. In meta-regression analyses, the proportion of patients with coronary artery disease was inversely related with LVEF improvement (P < .0001) whereas there was no association between the LVEF change and the proportion of patients with nonparoxysmal AF or the proportion of patients without AF recurrences during follow-up.

Conclusions

AF ablation in patients with systolic LV dysfunction results in significant improvement of LV function, but the extent of this improvement is heterogeneous. Patients with coronary artery disease seem to benefit less than patients with other underlying diseases. These results may be explained by patient selection.     

Limited atrial compensation to reduced early diastolic filling in hypertensive patients with advanced left ventricular hypertrophy: A Doppler echocardiographic study

Summary To assess atrial contribution to left ventricular (LV) filling in hypertension, we studied, using pulsed Doppler echocardiography, 22 hypertensive patients without apparent LV hypertrophy (LVH), 12 hypertensive patients with LVH, and 24 age-matched normal subjects. From mitral flow velocity waveform, we determined peak velocity of early diastolic filling flow (peak E), peak velocity of late diastolic filling flow (peak A), and the peak A/peak E ratio (peak A/peak E). Peak E decreased in hypertensives without apparent LVH and showed a further decrease in hypertensives with LVH compared with normal subjects (57±8 [mean ± SD];P<0.001, 46±7;P<0.0001, vs 65±10 cm/s). On the other hand, peak A/peak E increased in hypertensives without apparent LVH, and greatly increased in hypertensives with LVH (1.06±0.14;P<0.001, 1.40±0.29;P<0.0001, vs 0.79±0.21). However, increased peak A was not significantly different between the hypertensive groups (60±8 vs 64±8; NS, both;P<0.001 vs 50±10 cm/s for normal subjects). In hypertensives, we found no significant correlation between peak A and the wall thickness index (WTI, determined as mean LV wall thickness normalized by LV diastolic dimension), whereas peak E was significantly correlated with WTI (r=–0.65;P<0.001). Our findings indicate that atrial contraction can not fully compensate the decrease in early diastolic filling caused by advanced LVH. We conclude that atrial compensation for reduced early diastolic filling is limited in hypertensive patients with advanced left ventricular hypertrophy.