Reduction In Left Ventricular Dimensions Research Articles

UNPREDICTABLE IDENTIFICATION OF A TITIN MUTATION IN A YOUNG PATIENT PRESENTING WITH INFLAMMATORY CARDIOMYOPATHY

Abstract Case Presentation A 23 years old patient, affected by type 1 diabetes, presented with fever, dyspnea and bilateral peripheral edemas. In the last week he received antibiotic treatment for a persistent dry cough and sore throat, and became symptomatic for exertional dyspnea from three days. His mother died at the age of 40 for sudden cardiac death. Blood pressure and oxygen saturation were normal: the ECG showed sinus tachycardia with symmetric negative T waves in all precordial leads. High sensitivity troponin T was 0.01 mcg/L (normal value < 0.014 mcg/L). All remaining blood tests were normal, except for CRP that was slightly elevated. His echocardiogram revealed left ventricular (LV) remodelling and dilation, severely reduced LV ejection fraction (LVEF 20%) with global hypokinesia, more pronounced at the level of the anterior wall, interventricular septum and apex and a dilated right ventricle (RV) with reduced systolic function. Cardiac magnetic resonance (CMR) confirmed severe biventricular disfunction (LVEF 19%; RVEF 23%) and showed a small area of subepicardial inferior junctional late gadolinium enhancement (LGE). The patient underwent an endomyocardial biopsy that showed a lymphocytic virus–negative myocarditis. Given his known type 1 diabetes, steroid treatment was not considered and anakinra was started. The patient was discharged after two weeks with a slight amelioration of the LV function (LVEF 27%), on optimal heart failure therapy and anakinra. At six months he was in NYHA class II and CMR showed slight reduction in LV dimensions and improvement of the LV and RV function (LVEF 39%; RVEF 45%), with no changes in the LGE pattern. A genetic test was performed and revealed two titin gene mutations, both categorized as likely pathogenic (TTN c.[11831T>A]; c.[72510_72517delGACAAATG]), responsible for a genetic form of dilated cardiomyopathy. Conclusion The present case suggests that in young patients presenting with clinical or histological diagnosis of myocarditis, genetic testing for cardiomyopathies should be considered especially in presence of a positive family history for sudden death or an incomplete recovery of the LV function at follow–up. Identification of a gene mutation in these patients allows a more tailored risk stratification of the index case and a proper management of the entire family.

ELUCIDATE Trial: A Single-Center Randomized Controlled Study.

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. The ELUCIDATE trial was a prospective, open-label, randomized, active-controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add-on or standard-of-care group. Speckle-tracking echocardiography-based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53-2.84]; P=0.005), LV end-systolic volume (5.51 mL [95% CI, 0.86-10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42-6.09]; P<0.0001) compared with standard of care in absolute mean differences. Dapagliflozin add-on therapy led to a significant LV global longitudinal strain increment (0.74% [95% CI, 1.00-0.49]; P<0.0001) and improved LV systolic and early diastolic strain rates (0.27/s [95% CI, 0.17-0.60]; and 0.11/s [95% CI, 0.06-0.16], respectively; both P<0.0001) but not in global circumferential strain. No significant changes were found in insulin resistance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, or other biomarkers at 6 months after the dapagliflozin administration. Dapagliflozin add-on therapy could lead to more favorable cardiac remodeling accompanied by enhanced cardiac mechanical function among patients with asymptomatic type 2 diabetes. Our findings provide evidence of the efficacy of dapagliflozin use for the primary prevention of diabetic cardiomyopathy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871621.

Characterization of heart failure patients with reverse left ventricular remodelling post-angiotensin receptor blockers/neprilysin inhibitors therapy.

AimsTo assess the effect of angiotensin receptor blockers/neprilysin inhibitors (ARNI) on left ventricular (LV) ejection fraction (LVEF) and LV dimensions in a real‐life cohort of heart failure and reduced ejection fraction (HFrEF) patients, while analysing patient characteristics that may predict reverse LV remodelling.Methods and resultsThe ARNI‐treated HFrEF patients followed at a single tertiary medical centre HF‐outpatient clinic were included in the study. Clinical and echocardiographic parameters were evaluated prior to ARNI initiation, and while on ARNI therapy, assessing patient characteristics associated with reverse LV remodelling. The cohort included 91 patients (mean age 60.5 years, 90% male) and 47 (52%) patients exhibited ARNI responsiveness, defined as an increase in LVEF during therapy. Overall, LVEF increased by 19% post‐ARNI (23.8 to 28.4%, P < 0.001). Subgroup analysis revealed several parameters associated with significant LVEF improvement, including baseline LVEF <30%, non‐ischaemic HF aetiology, lack of cardiac resynchronization therapy (CRT), better initial functional class and ARNI initiation within 3 years from HF diagnosis (P ≤ 0.001 for all). Significant reduction in LV dimensions was noted in patients with lower initial LVEF, non‐ischaemic HF and no CRT. Further combined subgrouping of the study population demonstrated that patients with both LVEF <30% and a non‐ischaemic HF gained most benefit from ARNI with an average of 51% improvement in LVEF (19.9 to 30%, P < 0.001).ConclusionsThe ARNI treatment response is not uniform among HFrEF patient subgroups. More pronounce reverse LV remodelling is associated with early ARNI treatment initiation in the course of HFrEF, and in those with LVEF <30%, non‐ischaemic HF and no CRT.

Effect of Left Ventricular Hyperenhancement in Magnetic Resonance Imaging on Reverse Remodeling After Mitral Valve Repair for Moderate Ischemic Mitral Regurgitation

We aimed to investigate cardiac magnetic resonance imaging (MRI)-derived predictors of a lack of left ventricular (LV) reverse remodeling after undersized mitral annuloplasty (uMAP) for moderate ischemic mitral regurgitation (IMR). We retrospectively reviewed 31 patients who underwent uMAP for moderate IMR and cardiac MRI evaluation between 2004 and 2017. Cardiac MRI evaluation included cine MRI LV and right ventricular volumetric measurements and gadolinium-enhanced MRI assessment of myocardial scarring. LV dimensions were assessed preoperatively, postoperatively, and at follow-up using serial transthoracic echocardiography, and the mid-term (median, 49 months) predictors of a lack of LV reverse remodeling were analyzed. At the mid-term follow-up (mean follow-up period: 85 ± 40 months), 15 patients exhibited reverse LV remodeling. The relative reduction in LV dimension at follow-up was negatively correlated with the preoperative number of LV segments with myocardial infarction (MI) (defined as an LV segment with >25% enhancement). The optimal cut-off for predicting a lack of reverse LV remodeling at follow-up was >5 LV segments with MI, with a sensitivity and specificity of 92% and 92%, respectively. This cut-off value also predicted all-cause mortality at follow-up, with a sensitivity and specificity of 88% and 67%, respectively. The presence of >5 LV segments with MI on gadolinium-enhanced MRI might be a useful predictor of lack of reverse LV remodeling and all-cause mortality outcomes after undersized mitral annuloplasty for moderate IMR.

New right bundle branch block after selective HIS bundle pacing, Two methods for correction

HIS Bundle Pacing (HBP) is considered the most physiologic pacing technique as it generates a physiological activation of both ventricles through synchronous ventricular depolarization of His bundle– Purkinje conduction system. Permanent HBP and Atrioventricular Node (AVN) ablation in patients with heart failure and atrial fibrillation were found to have an improvement in cardiac function and reduction of left ventricular dimensions [1]. We present case of paroxysmal atrial fibrillation and atypical atrial flutter that underwent HBP and AVN ablation. The patient developed a Right Bundle Branch Block (RBBB) following his AVN ablation with widening of QRS duration to 148 msec. We managed to correct this and restore a narrow QRS by two different mechanisms: 1. Programming the Interventricular (VV) delay to 20 msec (His pacing first followed by septal RV pacing through a back-up lead, 2. Unipolar pacing of the HIS lead with different configuration. By both methods, QRS duration was reduced to 108-110 msec with restoration of physiologic biventricular pacing. To the best of our knowledge, this has not been reported before. Keywords: atrial fibrillation; his bundle pacing; ablate; pace.

Thiamine mediated reversal of left ventricular dysfunction in patients with alcoholic cardiomyopathy

This study aimed to evaluate the effect of thiamine supplementation on left ventricular (LV) systolic function in patients of alcoholic cardiomyopathy(ACM) presenting with acute heart failure(HF). 11 newly diagnosed patients were included. They were treated with 3 days of intravenous(IV) therapy with thiamine followed by oral supplementation. LVEF was 30% at baseline which improved by 45% and 53% along with reduction in LV dimensions over 3 and 6 months respectively. The study suggests the benefit of thiamine supplementation on LVEF in ACM patients with HF.

Changes in Cardiac Structure and Function Before and After Renal Transplantation: A Longitudinal Study

BackgroundEnd-stage renal disease is a major risk factor for cardiovascular disease. Kidney transplantation (KT) may lead to reversal of these cardiac changes. MethodsEchocardiographic changes in cardiac structure and function were recorded in 30 patients with end-stage renal disease before KT, and 3 months and 6 months after KT. Patients with ischemic heart disease and valvular heart disease were not included. ResultsThirty patients with a mean age of 34±12 years were studied, and 28 (93%) were male. Mean duration of hemodialysis (none on peritoneal dialysis) was 9.18±8.39 months. There was significant improvement in echocardiographic parameter of cardiac morphology and the cardiac systolic and diastolic functions after KT. ConclusionsThis longitudinal prospective study found significant regression of left ventricular hypertrophy within 6 months after renal transplant. There was also an improvement in ventricular functions on echocardiography. The improvement in hemoglobin shows linear correlation with reduction in left ventricular dimension and improvement in left ventricular functions.

Sex-Associated Differences in Cardiac Reverse Remodeling in Patients Supported by Contemporary Left Ventricular Assist Devices

Women differ from men in their left ventricular (LV) structure, function and remodeling with age and diseases. The LV assist device (LVAD) unloads the LV and reversely remodels the heart. We sought to define the effects of sex on longitudinal reverse remodeling after LVAD implantation. Cardiac structure and function were assessed by serial echocardiograms. Mixed effect regression models were constructed to assess the independent contribution of sex to longitudinal changes in cardiac structure and function. A total of 355 consecutive patients with advanced heart failure received continuous flow LVADs between 2006 and 2016. The average age was 56 ± 13 years, 73% were men, and 67% were black. Early (within 3 months) after LVAD implantation, women had a greater reduction in LV dimensions and a greater increase in LV ejection fraction compared with men. These differences were independent of age, body surface area, device type, or ischemic etiology of heart failure. At long-term follow-up, LV dimensions increased slightly over time in women compared with men, but overall, earlier changes were maintained. Women had significantly more favorable longitudinal changes in cardiac structure and function in response to LV unloading compared with men. Understanding the cause of sex difference in reverse remodeling after LVAD may help to devise novel therapeutic strategies for women with advanced heart failure.

P1523 Impact of different techniques for mitral valve repair on left ventricular function: a 2D/3D echocardiographic analysis

Abstract Funding Acknowledgements None Aim Different surgical techniques are available for mitral valve (MV) repair in patients with degenerative severe mitral regurgitation (MR). Leaflet resection (LR) and neochordoplasty (NP), both including ring annuloplasty (RA), are the most frequently performed techniques for posterior mitral leaflet prolapse/flail repair. Despite NP technique is supposed to preserve LV physiology more than LR, it is unclear which technique provides the best haemodynamic pattern. In the present study, the results of the two different surgical techniques in terms of left ventricular (LV) dimension and function are investigated. Methods 23 consecutive patients who underwent MV surgical repair were enrolled. All patients underwent, before surgery and after 8 ± 2 months, 2D and 3D echocardiography with automatic (Heart Model, Philips) assessment of LV volumes and ejection fraction (EF), left atrial (LA) volume, right ventricular (RV) dimension and function, pulmonary artery systolic pressure (PASP), MR, tricuspid regurgitation (TR) and MVPG quantification. MR was corrected using 1) NP with polytetrafluoroethylene sutures and 2) triangular LR, both with RA. Patients were divided in 2 groups according to the surgical technique. Results: techniques were able to successfully correct MR. There were no significant differences in baseline echocardiogram and demographic characteristics between the two groups. There were no significant differences in terms of post-surgical MVPG between the two groups. In all patients a trend in reduction in LV dimension at follow-up was observed, but it was statistically significant only in NP patients (pre-surgical EDV 150 ± 41 VS post-surgical EDV 100 ± 27 ml, p = 0.03). Conclusions Both MV repair techniques showed a successful MV repair and an improvement in LV volumes at follow-up, especially in NP group. Further perspective studies are necessary to demonstrate the hypothesis of more physiological haemodynamic pattern associated with NP techniques. Echo parameters pre VS post MV Repair Parameter pre post p value LVEDV RN (ml) 150 ± 41 100 ± 27 0.03 LVESV RN (ml) 58 ± 20 46 ± 14 NS LVEF RN (%) 58 ± 8 55 ± 7 NS LVEDV RR (ml) 160 ± 58 118 ± 31 NS LVESV RR (ml) 62 ±11 51 ±13 NS LVEF RR (%) 59 ± 8 57 ± 4 NS EDV: end-diastolic volume, ESV: end-systolic volume, EF: ejection fraction, RN = Ring + Neochordae; RR= Ring + Resect.

Beneficial effects of ivabradine in patients with heart failure, low ejection fraction, and heart rate above 77 b.p.m.

AimsIvabradine has been approved in heart failure with reduced ejection fraction (HFrEF) and elevated heart rate despite guideline‐directed medical therapy (GDMT) to reduce cardiovascular (CV) death and hospitalization for worsening HF. The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa, and Australia. Patient‐reported outcomes (PROs) including symptoms, quality of life, and global assessment are considered of major interest in the global plan of care of patients with HF. However, the specific impact of GDMT, and specifically ivabradine, on PRO remains poorly studied. In the subgroup of patients from the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) who had heart rate above the median of 77 b.p.m. (pre‐specified analysis) and for whom the potential for improvement was expected to be larger, we aimed (i) to evaluate the effects of ivabradine on PRO (symptoms, quality of life, and global assessment); (ii) to consolidate the effects of ivabradine on the primary composite endpoint of CV death and hospitalization for HF; and (iii) to reassess the effects of ivabradine on left ventricular (LV) remodelling.Methods and resultsComparisons were made according to therapy, and proportional hazards models (adjusted for baseline beta‐blocker therapy) were used to estimate the association between ivabradine and various outcomes. In SHIFT, n = 3357 (51.6%) patients had a baseline heart rate > 77 b.p.m. After a median follow‐up of 22.9 months (inter‐quartile range 18–28 months), ivabradine on top of GDMT improved symptoms (28% vs. 23% improvement in New York Heart Association functional class, P = 0.0003), quality of life (5.3 vs. 2.2 improvement in Kansas City Cardiomyopathy Questionnaire overall summary score, P = 0.005), and global assessment [from both patient (improved in 72.3%) and physician (improved in 61.0%) perspectives] significantly more than did placebo (both P < 0.0001). Ivabradine induced a 25% reduction in the combined endpoint of CV death and hospitalization for HF (hazard ratio 0.75; P < 0.0001), which translates into a number of patients needed to be treated for 1 year of 17. Patients under ivabradine treatment demonstrated a significant reduction in LV dimensions when reassessed at 8 months (P < 0.05).ConclusionsIn patients with chronic HFrEF, sinus rhythm, and a heart rate > 77 b.p.m. while on GDMT, the present analysis brings novel insights into the role of ivabradine in improving the management of HFrEF, particularly with regard to PRO (ISRCTN70429960).

Management of moderate ischemic mitral regurgitation: revascularization alone versus revasularization and mitral valve repair

Background Ischemic mitral regurgitation (IMR) is a frequent condition post-myocardial infarction. Management of moderate myocardial infarction is still debatable, with adding mitral valve repair (MVR) to coronary artery bypass grafting (CABG) being questionable. Aim To compare echocardiographic and clinical outcome of moderate IMR treated by revascularization alone versus another group of patients treated by revascularization and MVR. Patients and methods Forty consecutive patients with ischemic heart disease with moderate IMR undergoing on-pump CABG are randomly selected. They were divided into two groups: group I (20) had CABG+MVR, group II (20) had only CABG; echocardiography was done postoperatively and after 6 months for both groups. Results Our study revealed improvement in the grade of mitral regurgitation (MR) in both groups which was more evident and significant in group I than II with 11 (61%) of group I showing complete resolution of MR versus 0 patients in group II which was highly statistically significant (P=0.0001). Follow-up after 6 months, there were significant reduction in the New York Heart Association functional class as well as the mean grade of MR in group I versus group II, (P=0.004), with nine (50%) patients in group I against two (11%) patients in group II had complete resolution (P=0.004). We found also significant reduction in left ventricular dimensions and function. Conclusion MVR can be performed safely, concomitantly with coronary artery bypass grafting in patients who have moderate IMR.

Cardiac Consequences of Autonomic Dysreflexia in Spinal Cord Injury.

Autonomic dysreflexia (AD), which describes episodic hypertension, is highly prevalent in people with spinal cord injury (SCI). In non-SCI, primary hypertension depresses cardiac contractile reserve via β-adrenergic mechanisms. In this study, we investigated whether AD contributes to the impairment in cardiac contractile function that accompanies SCI. We induced SCI in rodents and stratified them into sham, SCI, or SCI plus repetitive induction of AD. At 6-week post-SCI, we assessed cardiac function using in vivo (speckle-tracking echocardiography), ex vivo (working heart), and molecular approaches (Western blot). We also provide unique translational insight by comparing the relationship between the number of daily AD events and cardiac function in 14 individuals with cervical SCI. We found SCI and SCI plus repetitive induction of AD exhibited a reduction in left ventricular dimensions at 6-week post-SCI versus preinjury (P<0.049). Compared with sham, SCI exhibited a reduction in peak radial strain along with a down and rightward shift in the Starling curve (P<0.037), both of which were further depressed in SCI plus repetitive induction of AD (P<0.042). In response to β-adrenergic stimulation, SCI plus repetitive induction of AD exhibited an attenuated increase in contractile indices (P<0.001), despite no differences in β-receptor expression within the left ventricle. Our clinical data confirm our experimental findings by demonstrating significant associations between the number of daily AD events and markers of systolic and diastolic function along with left ventricular mechanics. Here, we provide the first evidence from a translational perspective that AD exerts insidious effects on cardiac function in rodents and humans with SCI.

Hospital-based and telemonitoring guided home-based training programs: Effects on exercise tolerance and quality of life in patients with heart failure (NYHA class III) and cardiac resynchronization therapy. A randomized, prospective observation.

Cardiac resynchronization therapy with defibrillator function (CRT-D) along with an optimal medical therapy improves symptoms, cardiac efficiency, quality of life (QoL) and prognosis in patients with heart failure (CHF). The aim of the study was to assess effects of hospital-based and home-based/telemonitoring exercise training. MethodsThe prospective, randomized study was conducted in 52 patients (pts), aged 45–75years (mean 62±9.3), with CHF of ischemic or another etiology, NYHA class III and implanted CRT-D. Group CRT-Ex (n=26) underwent initial exercise training in the hospital setting and continued training program at home with telemonitoring 5 times a week for 8weeks. The CRT-control group (n=26) consisted of patients who had hospital rehabilitation, but no training program after discharge. ResultsNo differences between the groups in CHF etiology, comorbidities, medical therapy and in any of spiroergometry (CPX) parameters at baseline were observed. After 3–4months the CRT-Ex group achieved better results in VO2 peak, VCO2 peak and treadmill test duration. But after 12months the measurements returned to the baseline values. No significant differences were observed directly between two groups in distances of 6-MWT at baseline, at 3–4months and at 12months. Echocardiographic evaluation showed significant reduction of left ventricular dimensions and improvement in the left ventricular ejection fraction (EF), in both groups (25.3±7.4% to 28.9±9.1%, CRT-Ex group, p=0.0213 and 24.9±7.2% to 31.7±10.6%, CRT-Control group, p=0.0001). Significant improvement in all domains of QoL was observed in the CRT-Ex group, while the CRT-Control pts declared only higher energy levels and less pain. Intensity of telemonitoring guided home-based exercise training was low. In the 12- and 18-months follow-up there were no differences in the ICD-interventions, mortality or hospitalization rates between the groups. ConclusionsA structured exercise training program in the hospital and home-based with telemonitoring was safe option of additional treatment and improved directly physical fitness and, quality of life in patients with NYHA III CHF and CRT-D. However these effects haven't been sustained in longer period of time and had no impact on prognosis.

Preoperative ejection fraction determines early recovery of left ventricular end-diastolic dimension after aortic valve replacement for chronic severe aortic regurgitation

BackgroundIn patients with chronic severe aortic regurgitation (AR), aortic valve replacement (AVR) has been proved to promote left ventricular (LV) remodeling, especially LV end-diastolic dimension (LVEDD) reduction. However, there is little research whether postoperative LVEDD could return to normal parameter after AVR. The objective of this study was to determine predictors for the recovery of dilated LVEDD early after AVR. MethodsThe echocardiographic data of 105 patients, who underwent AVR for chronic pure AR between January 2005 and December 2011, were analyzed at the preoperative (3–7 d), early (6–8 mo), and late (2-y) postoperative stages, retrospectively. According to the baseline level, LVEDD >70 mm or LV end-systolic dimension (LVESD) >50 mm or LVESD index >25 mm/m2 were defined as severe LV dilation. Patients were then categorized into two groups (group 1: severe LV dilation; group 2: nonsevere LV dilation). ResultsIn all patients, four-fifth of the reduction in LV dimension occurred at early (6–8 mo) postoperative stage. The patients in both groups had significant decreases in the LVEDD and LVESD early after AVR, with an additional but insignificant reduction at late postoperative stage. The ejection fraction (EF) in both groups significantly increased at either early or late stage. However, the LVEDD and LVESD in group 1 were larger than those in group 2, and the EF in group 1 was lower than that in group 2 at early postoperative stage. By multivariate analysis, we found that the preoperative EF was a good predictor for the recovery of dilated LVEDD early after AVR (P = 0.009). Receiver-operating characteristics analysis showed that EF >52% was the best cut-off value for the recovery of LVEDD. ConclusionsIn patients with chronic pure AR, preoperative EF may be a good predictor for successful recovery of dilated LVEDD early after AVR.

Passive hind‐limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury

Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day(-1), 5 days week(-1) for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.

Immunosuppressive therapy in myocarditis.

Although there is general agreement on the favorable effect of immunosuppression in eosinophilic, granulomatous, giant-cell myocarditis and in lymphocytic myocarditis associated with connective tissue disorders and with rejection of a transplanted heart, its therapeutic role in lymphocytic inflammatory cardiomyopathy (ICM) is still debated. Previous retrospective studies reported a relevant clinical benefit in 90% of patients with virus-negative ICM and no response or cardiac impairment in 85% of those with virus-positive ICM following immunosuppression. Other studies identified cardiomyocyte HLA upregulation as an additional indicator of ICM susceptibility to immunosuppressive therapy. Recently in a single-center randomized prospective double-blind trial using a combination of prednisone and azathioprine in addition to supportive treatment in 85 virus-negative ICM patients, a significant improvement in left ventricular (LV) ejection fraction and a significant reduction in LV dimensions in 88% of 43 treated patients compared with 42 patients receiving placebo who showed a cardiac impairment in 83% of cases (TIMIC study) was reported. These data confirm the efficacy of immunosuppression in virus-negative ICM. Lack of response in 12% of cases suggests the presence of unscreened viruses or mechanisms of damage and inflammation not susceptible to immunosuppression. Recovery of cardiac function in responders to immunosuppression was associated with inhibition of cardiomyocyte death, increased cell proliferation and with newly synthesized contractile material.

Heart failure with preserved ejection fraction (diastolic heart failure)

Diastolic heart failure, which is also called as heart failure with preserved ejection fraction, is a clinical syndrome in which patients have signs and symptoms of heart failure, normal or near normal left ventricular ejection fraction (≥ 50%) and evidence of diastolic dysfunction. Recent epidemiological studies have demonstrated that more than half of all heart failure patients have diastolic heart failure. The syndrome is more common in women than in men and the prevalence increases with age. Patients with diastolic heart failure form a fairly heterogeneous group with complex pathophysiologic mechanisms. The disease is often in association with other comorbidities, such as hypertension, diabetes mellitus or obesity. The diagnosis of diastolic heart failure is best achieved by two-dimensional and Doppler echocardiography, which can detect abnormal myocardial relaxation, decreased compliance and increased filling pressure in the setting of normal left ventricular dimensions and preserved ejection fraction. Unlike heart failure with reduced ejection fraction, there is no such an evidence-based treatment for heart failure with preserved ejection fraction, which would improve clinical outcomes. Thus, pharmacological therapy of diastolic heart failure is based mainly on empiric data, and aims to the normalization of blood pressure, reduction of left ventricular dimensions and increased heart rate, maintenance of normal atrial contraction and treatment of symptoms caused by congestion. Beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers may be utilized in patients with diastolic dysfunction, especially in those with hypertension. Beta-blockers appear to be useful in lowering heart rate and thereby prolonging left ventricular diastolic filling time, while diuretic therapy is the mainstay of treatment for preventing pulmonary congestion. Nonetheless, treatment of the underlying disease is also an important therapeutic approach. This review summarizes the state of current knowledge with regard to diastolic heart failure.

Sildenafil Therapy in Patients with Thalassemia and an Elevated Tricuspid Regurgitant Jet Velocity (TRV) On Doppler Echocardiography At Risk for Pulmonary Hypertension: Report From the Thalassemia Clinical Research Network

AbstractAbstract 1023 Introduction.Pulmonary hypertension (PH) is a complication associated with thalassemia syndromes, particularly thalassemia intermedia. There are limited data on the safety and efficacy of selective pulmonary vasodilators in this at-risk population. Methods.We evaluated the safety and efficacy of a 12-week prospective, phase 1/2 pilot scale study of sildenafil (100 mg TID) in ten b-thalassemia patients with elevated TRV on Doppler-echocardiography ≥ 2.5 m/s suggestive of PH risk. Patients were evaluated at baseline and at weeks 2, 4, 8 and 12 of sildenafil therapy, and six minute walk distance (6MWD), biomarkers of hemolysis, coagulation, inflammation and adhesion were assessed. Results.Our study population had an average age of 37±12.3 years, 8/10 were male, and 50% were thalassemia intermedia. Splenectomy prevalence was high (90%), and only 30% of patients were transfused since infancy. The mean pre-transfusion hemoglobin was 10.4±1.5 g/dL. A 12-week open-label trial resulted in a significant decrease in TRV by 13.3% (3.0±0.7 vs. 2.6±0.5m/s, p=0.04, Figure 1), improvements in left ventricular end systolic/diastolic volume (p≤0.02), diffusion capacity for carbon monoxide (DLCO, p=0.003) and a trend towards a reduced Borg Dyspnea Score and improved NYHA Functional class. No significant change in 6MWD was noted, although 6MWD correlated strongly with DLCO (ρ=0.72, p=0.03) suggesting that oxygen diffusion across the alveolar-capillary membrane was an important determinant of exercise capacity. Sildenafil was generally well tolerated, but most patients experienced anticipated transient headaches and visual/color disturbances associated with sildenafil use. One patient withdrew from the study due to worsening dyspnea. No other serious adverse events were reported. A strong direct correlation between total dose of sildenafil (mg) taken and % change in plasma NO metabolite concentration was observed (ρ =0.80, p=0.01). A significant increase in plasma and erythrocyte arginine concentration occurred, without an associated change in plasma arginase activity/concentration, nitric oxide metabolites or vascular endothelial growth factor. However arginase concentration was elevated in this cohort similar to prior reports, and correlated inversely to hemoglobin (ρ=-0.41, p=0.01), and directly to ALT (ρ=0.40, p=0.004), AST (ρ=0.38, p=0.04), left ventricular end systolic volume (ρ=0.77, p=0.001), and end-diastolic volume (ρ=0.79, p=0.001). Conclusion.Our study suggests that sildenafil is safe and may improve cardiopulmonary hemodynamics in patients at risk for PH, however improved exercise capacity as reflected by an improved 6MWD was not observed. The reduction in left ventricular dimensions is promising, and could reflective of either increased inotropy or chronotropy, or decreased systemic afterload. This is also the first report of an influence of sildenafil on diffusion capacity of the lungs in patients with thalassemia and the first description of increased plasma and erythrocyte arginine concentration after sildenafil therapy. Given the association of arginine bioavailability with long-term survival in cardiovascular disease, this is an unexpected effect of sildenafil that warrants further investigation. These data support the need for further clinical trials evaluating the use of sildenafil in thalassemia. [Display omitted] Disclosures:Taher:Novartis: Research Funding, Speakers Bureau.

Immunosuppressive therapy in virus-negative inflammatory cardiomyopathy

While there is general agreement on the favorable impact of immunosuppression in eosinophilic, granulomatous, giant cell and lymphocytic myocarditis and with inflammatory myocardial disease associated with connective tissue disorders or with rejection of a transplanted heart, its therapeutic role in the treatment of lymphocytic inflammatory cardiomyopathy (ICM) is still debated. Previous retrospective studies reported a relevant (≥ 10% left ventricular ejection fraction) clinical benefit in 90% of patients with virus-negative ICM and no cardiac impairment in 85% of patients with virus-positive ICM following immunosuppression. Some studies identified cardiomyocyte HLA up-regulation as an additional indicator of ICM susceptibility to immunosuppressive therapy. Recently in a single-center randomized prospective double-blind trial using a combination of prednisone (1mg/kg per day for 4 weeks followed by 0.33mg/kg per day for 5 months) and azathioprine (2mg/kg per day for 6 months) in addition to supportive treatment in 85 virus-negative ICM patients, a significant improvement of left ventricular ejection fraction and a significant reduction of left ventricular dimensions in 88% of 43 treated patients was reported when compared to 42 patients receiving placebo who showed a cardiac impairment initially in 83% of cases (TIMIC study). These data confirm the efficacy of immunosuppression in virus-negative ICM. The lack of response in 12% of cases suggests that the missing response might be due to the presence of viruses which were not screened for or to mechanisms of damage and inflammation not susceptible to immunosuppression. The recovery of cardiac function in responders to immunosuppression was associated with the inhibition of cardiomyocyte death, an increase of cell proliferation and with newly synthesized contractile material.

Early Outcomes Using the Florida Sleeve Repair for Correction of Aortic Insufficiency due to Root Aneurysms

The Florida sleeve procedure is a simplified valve-sparing technique for repair of functional type I aortic insufficiency associated with root aneurysms. Midterm outcomes are reported, including standard echocardiographic measurements. The study included all patients undergoing the Florida sleeve procedure who had at least 2 years of postoperative echocardiographic follow-up. Data were acquired preoperatively and postoperatively at 1 week and 1, 2, and 3 years. Measurements analyzed included left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and degree of aortic insufficiency. Complete echocardiographic data for a mean 32 +/- 6.3 months after repair were available for 18 patients. Mean LVEDD decreased from 51.6 +/- 7.4 to 49.7 +/- 6.3 mm at 1 week (p = 0.05) and 47.1 +/- 6.3 mm at 1 year (p = 0.008), and remained unchanged at 47.2 +/- 6.6 and 47.1 +/- 5.0 mm at 2 and 3 years. Mean LVESD decreased from 35.2 +/- 7.6 to 32.9 +/- 7.0 mm at 1 week (p = 0.002) and 30.7 +/- 5.6 mm at 1 year (p < 0.001), and remained unchanged at 30.9 +/- 6.2 and 31.7 +/- 4.9 mm after 2 and 3 years. The mean grade of aortic insufficiency decreased from 2.61 +/- 0.78 to 1.39 +/- 0.85 mm at 1 week (p < 0.001) and remained 1.39 +/- 0.84 mm at 1 year. Aortic insufficiency increased to 1.72 +/- 0.89 (p = 0.03) at 2 years and decreased to 1.67 +/- 0.50 (p = 0.59, from 1 week postoperatively) at 3 years. The sustained reduction of left ventricular dimensions 3 years after operation suggests the Florida sleeve procedure is a durable valve repair. A minor increase in the degree of aortic insufficiency warrants close follow-up, but the absence of an increase of LVEDD supports continued use of the procedure in closely studied series.