It is well known that an autonomic dysfunction is present in heart failure setting as a neuronal uptake of norepinephrine is impaired in the failing myocardium. Reduction in sympathetic nervous function in the heart, measured by reduced myocardial uptake of 123I-MIBG, is an indicator of poor prognosis for heart failure patients. The aim of this paper was to investigate the role of 123I-MIBG scintigraphy in evaluating the need of implantable cardioverter defibrillator (ICD) and the response to cardiac resynchronization therapy (CRT) in heart failure patients. For this purpose scientific literature data on these topics were reviewed. Based on literature data, 123I-MIBG scintigraphy seems to be a useful tool to assess which patients may benefit most from an ICD implantation to reduce the risk of ventricular arrhythmia or sudden cardiac death. Furthermore, 123I-MIBG scintigraphy seems to predict which patients will response to CRT with an improvement in left ventricular function.Iodine-123-metaiodobenzylguanidine ( Heart failure (HF) is characterized by alterations in myocardial sympathetic nerve activity; an increased sympathetic response is initially favorable by serving as compensation for decreased cardiac output, but as HF progresses, this response leads to deleterious neurohormonal and myocardial structural changes that worsen the condition and increase the likelihood of arrhythmias and cardiac death .123I-MIBG) scintigraphy provides a noninvasive tool for the investigation of cardiac sympathetic innervation; this technique can also demonstrate drug-induced changes in cardiac adrenergic activity [Myocardial innervation imaging with iodine 123 metaiodobenzylguanidine  and 4 hours (delayed image) after radiopharmaceutical injection with the patient lying in the same supine position. Tomographic (SPECT) images are usually performed after early and delayed planar imaging .123I-MIBG uptake is semiquantified by calculating the heart to mediastinum ratio (H/M), after drawing regions of interest (ROI) over the heart and the upper mediastinum in the planar anterior view. Average counts per pixel in the myocardium are divided by average counts per pixel in the mediastinum [iastinum . The myoiastinum .123I-MIBG scintigraphy [The delayed H/M ratio reflects the relative distribution of sympathetic nerve terminals, offering global information about neuronal function resulting from uptake, storage, and release. The WR reflects the neuronal integrity or sympathetic tone . Impairetigraphy .123I-MIBG uptake is characterized by a low interindividual and a within-subject variability [123I-MIBG scintigraphy has become a valuable tool to provide information regarding the potential and actual benefit of pharmacological treatment in patients with HF [Since semiquantitative analysis of myocardial iability , 123I-MI with HF .Implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) are also useful therapeutic options in patients with HF. ICDs are dedicated to pacing and/or defibrillating lethal cardiac arrhythmias, whereas CRT improves the electrical dyssynchrony found in many patients with HF and thereby can improve mechanical dyssynchrony leading to increased left ventricular function.123I-MIBG scintigraphy in HF patients referred for ICD or CRT.The purpose of this paper is to review published scientific data regarding the clinical usefulness of 123I-MIBG scintigraphy can help to estimate the prognosis and to monitor the effects of therapeutic interventions in HF patients [Several studies have shown that the assessment of the cardiac autonomic state with patients –14.123I-MIBG imaging, was associated with adverse cardiac outcomes in 112 patients with HF and a reduced left ventricular ejection fraction (LVEF). After a mean followup of 27 ± 20 months, the only independent predictors for mortality were low myocardial 123I-MIBG uptake (P < 0.01) and LVEF (P = 0.02) [First, Merlet et al.  demonstr = 0.02) .123I-MIBG scintigraphy was 1.51 ± 0.30 in patients who had major cardiac events (MCEs) and 1.97 ± 0.54 in patients without MCEs (P < 0.001). When an optimum H/M was set at 1.75, two-year event-free survival was 62% for H/M under this threshold and 95% for H/M greater than or equal to 1.75 (P < 0.0001). Moreover, H/M and LVEF were the only significant predictors of MCEs. The authors confirmed the prognostic value of 123I-MIBG scintigraphy in HF patients, and its potential to identify a quantitative threshold that may help to estimate the risk of cardiac mortality and potentially fatal ventricular arrhythmias [Then, Agostini et al.  enrollinhythmias .123I-MIBG imaging for identifying symptomatic HF patients (NYHA class II/III and LVEF ≤35%) most likely to experience cardiac events. Among the 961 patients enrolled, 25% experienced events (median follow-up 17 months). The cardiac event risk (primary end point) was significantly lower for subjects with H/M ≥1.60. For H/M <1.60, 2-year probabilities of cardiac death and all-cause mortality were 11.2% and 16.1% versus 1.8% and 3.0% for the group with H/M ≥1.60. Significant contributors to the multivariable model were H/M, LVEF, brain natriuretic peptide (BNP), and NYHA functional class. 123I-MIBG imaging also provided additional discrimination in analyses of interactions between BNP, LVEF, and H/M. Moreover, 9% of the patients experienced either nonfatal arrhythmic events  or sudden cardiac death (n = 23). These combined “arrhythmic” events were significantly more common in subjects with H/M <1.60. ADMIRE-HF study provided prospective validation of the independent prognostic value of 123I-MIBG scintigraphy in the assessment of patients with HF [Recently, the ADMIRE-HF study  confirme123I-MIBG scintigraphy parameters are predictive of sudden cardiac death in patients with mild-to-moderate HF independently of LVEF [123I-MIBG and inducible ventricular tachyarrhythmias in patients with left ventricular dysfunction and previous myocardial infarction. These authors demonstrated that 123I-MIBG scintigraphy abnormalities are associated with lethal arrhythmias and may guide appropriate ICD implantation in patients affected by HF [Some clinical trials have demonstrated that  of LVEF . Kasama  of LVEF . Bax et  of LVEF  examineded by HF .123I-MIBG scintigraphy in patients with ICD was designed by Rigden et al. who demonstrated that ICD shocks did not cause any change in sympathetic nerve activity in 11 patients who underwent 123I-MIBG scans before and after ICD implantation [One of the first studies performed to explore any role of antation .Although the ICD has been shown to abort potentially fatal ventricular arrhythmias, identification of patients who will most benefit from this device remains difficult. Despite widespread use of ICDs, their cost and the fact that only a certain group of patients fully benefits from the devices require appropriate risk stratification of patients. In the last years several studies were designed in order to identify patients who will benefit most from an ICD .123I-MIBG imaging, as well as central autonomic tone with the use of heart rate variability (HRV) analysis, in patients with ICD. Test results were correlated with the occurrence of ICD discharges. Seventeen patients with previously implanted defibrillators were studied. Of these, 10 had at least 1 appropriate device discharge for ventricular tachyarrhythmias, whereas 7 had no discharge. Patients with a discharge had a significantly lower 123I-MIBG H/M, more extensive sympathetic denervation, and significantly reduced values for several HRV parameters [123I-MIBG imaging may help to select patients who would most benefit from an ICD by identifying those at increased risk for potentially fatal arrhythmias.Arora et al.  undertoorameters . This wa123I-MIBG uptake (quantified as H/M), plasma concentration of BNP, and LVEF. Patients were divided into 2 groups based on the presence (group A) or absence (group B) of appropriate ICD discharge and followed up for a 15-month period. Group A had a significantly lower level of cardiac 123I-MIBG uptake and a higher plasma BNP level than did group B. Univariate analysis revealed that plasmatic BNP levels, any medication, and late H/M were predictors of lethal cardiac events, whereas multivariate analysis showed that only late H/M was a significant predictor. Thus, the authors concluded that when combined with plasma BNP concentration or cardiac function, cardiac 123I-MIBG uptake is closely related to lethal cardiac events and can be used to identify patients who would benefit most from an ICD [Then, Nagahara et al.  investigm an ICD .n = 15) or dilated (n = 10) cardiomyopathy. One week after ICD implantation they underwent baroreflex sensitivity (BRS) evaluation, 24-h HRV assessment, and 123I-MIBG imaging. The mean patient followup was 32 ± 10 months. The frequency of fast ventricular arrhythmic episodes (FVAE) demonstrated a positive correlation to WR at 123I-MIBG imaging (P = 0.001). WR was also independent predictor of FVAE [Koutelou et al.  studied  of FVAE .123I-MIBG uptake in 60 patients with ICD who were prospectively followed with endpoints of appropriate ICD shocks or cardiac death. Cardiac 123I-MIBG was quantified as H/M. During a mean 29-month interval, ICD shock was documented in 30 patients (50%); three cardiac deaths were also observed in this group of patients. Patients with ICD shocks had a significantly smaller H/M than did those without ICD shocks [Nishisato et al.  quantifiD shocks .123I-MIBG imaging predicts ventricular arrhythmias causing appropriate ICD therapy (primary end point) and the composite of appropriate ICD therapy or cardiac death (secondary end point). One hundred sixteen HF patients referred for ICD therapy underwent 123I-MIBG scintigraphy and myocardial perfusion imaging before ICD implantation. During a mean followup of 23 ± 15 months, appropriate ICD therapy was documented in 24 (21%) patients and appropriate ICD therapy or cardiac death in 32 (28%) patients. Reduced myocardial 123I-MIBG uptake was an independent predictor for both end points [Boogers et al.  evaluated points .Current guidelines recommend CRT in HF patients who remain symptomatic in NYHA classes III-IV despite optimal pharmacological therapy, with LVEF <35%, LV dilatation (LV end diastolic diameter >55 mm) normal synus rhythm and wide QRS complex (≥120 ms) .Since CRT has been shown to reduce mortality due to reverse remodeling (reduction in ventricular volumes and improvement in systolic function), as well as to changes in sympathetic activity, some authors investigated whether CRT affects cardiac sympathetic nerve activity, and whether changes are related to CRT response –27 Tabl.123I-MIBG imaging [Higuchi et al.  evaluati imaging .P = 0.003), LVEF (P = 0.01), and H/M at 123I-MIBG imaging (P = 0.003). The H/M ratio and WR were associated with CRT response . Moreover, the H/M was the only independent predictor of CRT response (P = 0.01) [Nishioka et al.  studied 123I-MIBG imaging at followup when compared with baseline (P = 0.036) and also had a significantly lower WR at followup when compared with nonresponders (P = 0.002) [A similar trial was performed by Burri et al.  who repo= 0.002) .123I-MIBG imaging increased , whereas the WR was reduced  in 45 consecutive patients with HF who received CRT. Compared with nonresponders, CRT responders had a higher delayed H/M ratio  and a lower WR  at baseline [Cha et al.  demonstrbaseline .123I-MIBG imaging ≥1.6 were associated with a high frequency of LV functional improvement with a higher response rate [Moreover, Tanaka et al.  found thnse rate .123I-MIBG imaging significantly increased in the CRT responders but not in the nonresponders [Lastly Shinohara et al.  confirmesponders .Current indications for ICD implantation in primary prevention are referred to patients “with LV dysfunction due to prior myocardial infarction (MI) who are at least 40 days post MI, have LVEF less than or equal to 30% to 40%, are NYHA functional class II or III, are receiving optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than one year.” Moreover, ICD is recommended for primary prevention in “patients with non-ischemic dilated cardiomyopathy who have a LVEF less than or equal to 30% to 35%, are NYHA functional class II or III, who are receiving chronic optimal therapy and who have reasonable expectation of survival with a good functional status for more than 1 year.” Despite the current criteria, many subjects still die because they were considered low-risk patients .Conversely, many patients with an ICD device implanted after an abortive cardiac arrest or a life threatening ventricular tachycardia never experience appropriate ICD shock, and they are also exposed to unnecessary ICD shocks, device malfunction or infection, and higher risk of anxiety or depression. 123I-MIBG scintigraphy compared to other imaging modalities is the only able to evaluate the sympathetic cardiac innervations status in these settings and help to stratify patients who will most benefit from ICD implantation for primary prevention [Moreover, there are some cardiac diseases without left ventricular dysfunction which are associated with high risk of lethal arrhythmyas . evention .Heart rate variability is noted as the most sensitive marker of autonomic dysfunction; however, it seems, to be influenced by artifacts, rhythm disturbance, and noncardiac autonomic tone that makes it not reliable for stratifying HF patients.123I-MIBG scintigraphy is emerging as a powerful tool to assess prognosis in patients with HF and as an effective guide to evaluate appropriate ICD implantation in patients at high risk of sudden cardiac death. Most of the studies evaluated global cardiac 123I-MIBG activity, but regional SPET analysis is possible. However, it is difficult to reconstruct SPET data when global 123I-MIBG uptake is severely reduced; also, it is well known that MIBG uptake is underestimated at inferior and apical wall probably for attenuation or physiologic reason.123I-MIBG imaging for better selection of ICD candidates.Fewer data are available from scientific literature, and further clinical trials are needed to investigate the potential role of 123I-MIBG scintigraphy. Available data showed that CRT responders showed a rebalance in cardiac autonomic function as structural reverse remodeling may also be accompanied by reverse modulation of the cardiac sympathetic system, with attenuation of the excessive sympathetic drive—associated with HF—and with rebalance of cardiac autonomic activity. For these reasons, 123I-MIBG scintigraphy may have a potential role in predicting response to biventricular pacing. However, all these cited studies have a small sample size of patients. Further larger clinical trials are needed to understand whether cardiac 123I-MIBG scintigraphy may have a role in selecting HF patients who will better respond to CRT.It is well known that biventricular pacing reduces ventricular dyssynchrony and improves LVEF. Moreover, several studies demonstrated that CRT improved cardiac sympathetic activity assessed by 123I-MIBG scintigraphy among different studies. Some efforts have been done to standardize this technique  and to contribute to its clinical implementation for prognostication of HF patients undergoing ICD and CRT [Another issue that needs to be further addressed is the heterogeneity of data acquisition and image analyses about  and CRT –31.123I-MIBG scintigraphy seems to be a useful tool in cardiac dysfunction to assess which patients may benefit most from an ICD implantation to reduce the risk of ventricular arrhythmia or sudden cardiac death. Moreover, 123I-MIBG scintigraphy seems to predict which HF patients will respond to CRT with an improvement in left ventricular function.


Heart failure is a common cardiovascular disease with high morbidity and mortality. Unlike western countries where heart failure is predominantly a disease of the elderly, in India it affects younger age group. Important risk factors include coronary artery disease, hypertension, diabetes mellitus, valvular heart disease and cardiomyopathies. Plasma brain natriuretic peptide levels are helpful in the diagnosis of heart failure. Echocardiography is the primary imaging modality of choice, through recently cardiac magnetic resonance imaging (MRI) has been found to play an increasing role. Aim of management is to improve symptoms & enhance survival. Diuretics are important in relieving symptoms. Beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers and adosterone antagonists improve survival in patients with impaired systolic function. Device therapy including cardiac resynchronization therapy and implantable cardiac defibrillators, though expensive are useful in selected patients. Unlike in patients with systolic heart failure where several therapies have been shown to improve survival, clinical trial results in diastolic heart failure have been disappointing and therapy in these patients is restricted to symptom improvement and risk factor control. Therapies like stem cell therapy are being evaluated in clinical trials and appear promising. Early diagnosis and appropriate therapy helps in reversing the process of remodelling and clinical improvement in most of the patients. Heart failure (HF) is a common cardiovascular condition with increasing incidence and prevalence2Heart failure is third most common cardiovascular disease in the US affecting 2 per cent of the U.S. population, or almost 5 million people2In India, we do not have data regarding the exact prevalence and incidence of heart failure. With higher propensity for cardiovascular diseases and ageing population the burden of CHF is likely to be higher in comparison to the western population. Therefore, there is an urgent need to have HF registries in the secondary, tertiary care centers and at the national level. These will help and provide us the detailed information related to heart failure incidence, prevalence, aetiology and thus guide for adopting management strategies.Heart failure may be either predominantly systolic and diastolicIt is estimated that 40 to 50 per cent of patients with heart failure have preserved systolic function or a relatively normal left ventricular ejection fraction. Although such hearts contract normally, relaxation is abnormal. Cardiac output, especially during exercise is limited by the abnormal filling characteristics of the ventricles. These abnormally high filling pressures lead to pulmonary congestion, dyspnoea and oedemaPatients with diastolic heart failure are typically elderly, often female, obese and frequently have hypertension and diabetes. Mortality among these patients may be as high as that among patients with systolic heart failure, and the rates of hospitalization in the two groups are similarThe diagnosis of heart failure is mainly clinical but various investigations help us to understand the underlying cause and assessment of severity of HF. Investigations may help in doubtful cases especially when the clinical presentation is complicated by underlying lung disease.The classical clinical symptoms of heart failure are exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, fatigue and the signs are elevated jugular venous pressure, pulmonary rales, third heart sound and peripheral oedema. No single symptom or sign is pathognomic of heart failureSymptoms most sensitive for heart failure are exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoeaSigns of HF are also non-specific. These include basal crepitations, oedema, raised jugular venous pressure and hepatomegaly. These signs may be absent in patients with compensated heart failure or those on drug therapy. Features of right heart failure are not seen in 50 per cent of the patients with idiopathic dilated cardiomyopathy at initial diagnosisThe symptoms and signs bear an inconstant relationship to haemodynamic parameters including resting filling pressures, cardiac index and ventricular function in individual patients. Accurate functional classification remains problematic for individual patients. The NYHA (New York Heart Association) classification is limited by its poor reproducibility and relies exclusively on the presence and severity of symptoms rather any marker of ventricular remodelling.(i) careful history and physical examination, (ii) laboratory investigations including complete blood count, test of renal and hepatic functions, urinanalysis, electrocardiogram and chest x-ray, (iii) two dimensional and Doppler echocardiogram (iv) careful exclusion of coronary artery disease and thyroid disease in all patients, and (v) selective use of other diagnostic tests including serologic studies in selected patients based upon the clinical characteristics, risk factors, past medical and family historyThe ACC/AHA guidelines emphasize Electrocardiogram may help to indicate the underlying ventricular hypertrophy or evidence of coronary artery disease. Prolongation of QRS >120 ms occurs in approximately 30 per cent of patients with heart failure2224Cardiomegaly on skiagram has a sensitivity and specificity of 79 and 80 per cent respectivelyEchocardiogram is an important and simple tool to assess the ventricular function and underlying structural abnormality. Assessment of left ventricular systolic function in biplane Simpson’s method is routinely used in clinical practice. It is a valuable tool in measuring LV volumes and assessment of regurgitation. Echocardiography plays a vital role in the diagnosis of patients with heart failure, in part because the physical examination, electrocardiogram, and chest radiograph do not provide information that distinguishes diastolic from systolic heart failure28Radionuclide cardiac imaging is an excellent modality for assessment of ventricular volumes, geometry, diastolic function and myocardial perfusion. It is commonly used for assessment of myocardial viability. It can differentiate ischaemic and non-ischaemic cardiomyopathy.CT scan is useful in the evaluation of pericardial disease. Magnetic resonance imaging (MRI) is a validated technique for quantification of volumes, regurgitation and mass of the ventricles. It is a good modality for the assessment of myocardial viability. Myocardial diseases can be diagnosed accurately with cardiac MRI. Experience with cardiac MRI in India is limited since it is not cost-effective for routine evaluation. As coronary artery disease is the leading cause of heart failure, it is preferable to perform coronary angiogram in patients with left ventricular systolic dysfunction who are more than 35 yr of age even in the absence of clinical evidence of coronary artery disease.0 In dilated cardiomyopathies endomyocardial biopsy is helpful in identification of underlying myocarditis and cardiotropic viruses. In selected cases of infiltrative diseases it can be performed to diagnose the cause when other tests fail to reveal the exact aetiology of heart failure. The current recommendation for its use is in patients with new onset heart failure of < 3 months duration, haemodynamic compromise with or without a dilated ventricle, evidence of arrhythmias and failure to respond to usual care for 1 to 2 wk durationThe precursor of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is a pre-prohormone BNP, a 134-amino-acid peptide that is synthesized in the myocytes and cleaved to prohormone BNP of 108 amino acids. Prohormone BNP is cleaved by a circulating endoprotease into two polypeptides: the inactive NT-pro-BNP and BNP, a bioactive peptide37Primary prevention refers to identifying the risk factors for the development of heart failure and their prevention with an aim to reduce the incidence and burden of heart failure. As mentioned earlier the most important risk factors are hypertension, coronary artery diseases, diabetes mellitus and rheumatic heart diseases. Physical activity, dietary control and lifestyle modification can drastically bring down some of these modifiable risk factors and reduce the load of HF.Heart failure can be controlled by both primary and secondary means. Screening through population- based approach and high risk approach can yield satisfactory results and greater reduction in congestive heart failure. Screening for hypertension in individuals more than 30 yr of age and at interval of every 3-5 yr. Screening for diabetic individuals >45 yr of age and persons who have other risk factors for diabetes mellitus. Cholesterol screening (lipid profile) can be performed in individuals >45 yr of age and having risk factors for coronary artery diseases. Screening school children for identification of rheumatic heart diseases, as this is the age group frequently affected. These screening tests can be incorporated into the existing cardiovascular and chronic diseases control programmes. Health education and health promotion strategies are quite important in the success of theses programmes.There are two types approaches for prevention- high risk approach and population-based approach. High risk approach produces quicker results as seen in a Chinese study in a cohort of 2700 patients (>35 yr of age) with risk factors such as hypertension, diabetes mellitus and coronary artery disease in whom after a period of 3.5 yr the cumulative incidence of stroke was significantly lower in the intervention cohort than the control cohort The management of CHF depends largely on the setting where the patient presents. Almost 75 per cent of the population of India lives in rural areas. Health care in villages are largely provided by the primary health centers from the public health systems and by local primary care physicians who practice myriad form of systems including indigenous system.In the urban areas again a large proportion of health care is provided by private practitioners and vast expenditure is out of pocket. A few secondary and tertiary centres are available both in the public and private sectors. The management largely depends on where the patient is presenting .The general principles of treatment of heart failure include improvement of symptoms and survival. Every effort has to be made to identify the treatable causes of heart failure and treat the underlying condition. Specific therapy has to be initiated for anaemia, thyroid disorders and nutritional deficiencies. Aggressive management of systemic hypertension, diabetes mellitus, underlying coronary artery disease and surgical correction of valvular heart diseases should be carried out if indicated. Avoidance of alcohol and other toxins is necessary. The detailed algorithm for the diagnosis and management of heart failure is shown in Control of heart rate, reversion to normal sinus rhythm and anticoagulation appropriately are the usual measures adopted in patients with atrial fibrillation. In patients with anaemia, characterization of the type of anaemia is important. The role of erythropoietin in patients with normocytic, normochromic anaemia in HF is being evaluated. In bed ridden patients a possibility of pulmonary embolism has to be kept if heart failure worsens in spite of adequate therapy.Other therapies that are instituted in spite of the specific therapies are similar to all forms of heart failure.Exercise training: Exercise training improves exercise capacity and quality of life in patients with mild to moderate heart failure. Early trials have shown beneficial effects of aerobic exercises. More recent trials show that an element of resistance training improves muscle strength, bulk and endurance44Diet and nutrition: Heart failure patients are at increased risk of weight loss due to loss of appetite and hypercatabolic status. Adequate calorie intake and nutrients are part of the dietary programmes in these patients. Salt restriction according to symptoms is an essential component. Fluid balance has to be maintained. A supervised nutritional intervention was shown to improve clinical status and quality of life in heart failure patientsEducation and counselling: The physician and caregivers should educate the patients regarding the nature of the disease and take steps to prevent further progression of disease. Lifestyle modification and strict compliance to medication is important. Psychological support by the treating physicians boosts the confidence of patients.These are the main stay of therapy to relieve congestive symptoms. Three classes of drugs are available: loop diuretics, thiazide group and potassium sparing diuretics.Loop diuretics: Agents belonging to this group include furosemide, torsemide and bumetinide. These are most potent diuretics that act on the ascending loop of Henle. Recent data suggest that torsemide and bumetanide are more effective than furosemide in the treatment of advanced heart failure48Thiazide diuretics: These act by inhibiting the reabsorption of sodium and chloride from distal convulted tubule. Diuresis with these agents is modest and these are ineffective at glomerular filtration rate below 40 ml/minMetalozane belongs to the quinalozone sulphonamide group. It acts by inhibition of sodium reabsorption in the cortical collecting duct and proximal convoluted tubule. Its main advantage is its efficacy in reduced renal function.The beneficial role of β-blockers in the treatment of heart failure is well established. Agents commonly used in clinical practice are sustained release metoprolol, carvedilol, bisoprolol and nebivolol. Several large randomized placebo-controlled studies in patients with class II-IV heart failure in particular the MERIT-HF, COPERNICUS, CIBIS and COMET trials showed mortality and morbidity benefit with usage of β-blockersThe drugs that produce both venous and arterial dilatation are the preferred agents in heart failure as most forms of heart failure have elevated preload and after load. The ACEI acts on both the arterial and venous capacitance vessels. They act by inhibiting the production of angiotensin II as a consequence preventing the deleterious effects of angiotensin II through its action predominantly on the type 1 receptors. The levels of bradykinin are raised which result in the production of nitric oxide and other important endogenous vasodilatorsThere is a clear-cut and compelling evidence that all patients with heart failure and asymptomatic left ventricular dysfunction should receive ACE inhibitor therapy. Multiple well designed prospective randomized placebo-controlled trials, particularly CONSENSUS I, V-HEFT II and SOLVD showed improvement in symptoms and survival in patients with mild to severe heart failureWhich first- β-blockers or ACEI?: Historically the efficacy of ACEI in setting of heart failure was demonstrated in the early 1990s, well before the utility of β-blockers was understood. Thus therapy for heart failure is usually started with an ACE inhibitors and β-blockers added later. This practice is not based on any trial evidence but rather appears to be based simply on the historical factors. In fact there is a pathophysiologic basis for the theory that it may be appropriate to start treatment with a beta-blocker. The sympathetic nervous system is activated before the renin-angiotensin-aldosterone system in heart failure, and both systems are inhibited by beta-blockers. Moreover, sudden death, the most prevalent cause of death in early heart failure, is also reduced by β-blockers. The CIBIS III trial compared bisoprolol first and enalapril first regimens. There was no significant difference in the primary endpoint  between the two treatment strategiesIn the renin angiotensin aldoterone system, the action of the angiotensin converting enzyme produces angiotensin II from angiotensin I. There are other alternative pathways for the generation of angiotensisn II. They are the chymase, chymotrypsin, angiotensin generating enzyme and cathepsin D pathways. The ARBs act at the angiotensisn II receptor level blocking the downstream effects of angiotensin II. ARBs can be used in treatment of heart failure instead of ACE IIn heart failure the circulating levels of aldosterone are increased. The deleterious effects include endothelial dysfunction, increased oxidative stress, activation of matrix metalloproteinases, and activation of sympathetic nervous system. In conjunction with angiotensin II enzyme its effects are enhanced. The RALES study showed that spironolactone reduced mortality in severe heart failure patients treated with an ACE I with or without β-blockers by 30 per centDigoxin acts by inhibition of the sodium potassium adenosine triphosphatase enzyme and increases the intracellular Na. This drug is being used for more than a century in the treatment of heart failure. The randomized trials RADIANCE and the DIG trial showed significant reduction in hospitalizations for worsening heart failure but no reduction in mortality74Acute heart failure syndromes (AHFS) are often associated with reversible factors like ischaemia and the cardiac function can return to normal if these are corrected. If not appropriately treated, a vicious cycle is triggered that can lead to chronic heart failure and death. The goals of therapy thus include stabilization of the haemodynamic condition and correction of the underlying reversible factors.Based on the EFICA and OPTIMIZE HF studies the initiation of treatment in acute heart failure syndromes depend on the systolic blood pressureThese patients may need supplemental oxygen therapy to maintain oxygen saturation within normal range by increasing FiO2. In case, oxygen saturation is not maintained, non-invasive positive pressure ventilation (NIPPV) should be considered. NIPPV improves oxygen saturation, decreases the need for endotracheal intubation but does not appear to reduce mortality. Endotracheal intubation and invasive ventilation should be considered if the condition deteriorates.Some patients may also need temporary mechanical haemodynamic support with intra-aortic balloon pump or left ventricular assist device. Simultaneously, correction of the underlying cause is of primary importance.Most inotropic agents act by increasing the myocardial contractility through increase in intracellular cyclic adenylate monophosphate which ultimately leads to increased calcium in the sarcoplamic reticulum. Of these agents, the commonly used in clinical practice are dopamine, dobutamine, ephinephrine, norephinephrine, milrinone and enoximine. Of these inotropes, milrinone and enoximine are phosphodiesterase III inhibitors. Although inotropic agents temporarily stabilize the haemodynamic status, their long-term use is associated with increased mortality2Cardiac resynchronization therapy: Cardiac resynchronization therapy (CRT) is an established therapy in patients with LV systolic dysfunction and moderate to severe heart failure symptoms despite optimal medical therapy and evidence of wide QRS > 120 ms81Implantable cardiac defibrillator (ICD): Sudden cardiac death is responsible for 25 to 50 per cent of mortality in heart failure patients. The percentage of sudden deaths is higher in patients with mild to moderate heart failure as opposed to advanced forms where pump failure accounts for a larger percentage of deaths. The MADIT-II and SCD-HeFT trials confirmed the effectiveness of ICD for primary prevention in heart failure83Ventricular assist devices: Mechanical circulatory assist devices are used in both acute and chronic heart failure. They are used as a bridge to recovery, bridge to transplant or as permanent destination therapyAs coronary artery disease is one of the major causes of heart failure every effort has to be made to undertake complete revascularization after assessment of myocardial viability. In patient with valvular heart diseases repair or replacement as per recommendations and guidelines is helpful in prevention and treatment of heart failure. In patients with secondary or functional mitral regurgitation and ischaemic mitral regurgitation, valve repair surgery preserving the mitral apparatus is advocated. Other surgical modalities reshape the dilated ventricle to decrease the volume and stress on the ventricle. Partial left ventriculectomy (Batista procedure) is no longer popular due to poor long-term outcomes. Cardiac transplantation remains the gold standard therapy for end stage heart disease87Studies have demonstrated modest increase in LV ejection fraction and improvement in symptoms in patients with LV dysfunction of both ischaemic and non ischaemic aetiologyDisease management programmes (DMP) have been developed to standardize and optimize CHF treatment. These programmes focus on education of the patient and continuing support after hospital discharge. Studies have shown that these programmes have been shown to reduce mortality and hospitalization rates, improve quality of life and economically beneficial.Telemedicine is being increasely used in India in the diagnosis and management of disease to people out of reach in remote areas. Telemonitoring can also be effectively used in monitoring heart failure patients. By allowing clinical data to be collected without the need for face to face contact with the patients, telemonitoring facilitates easy access for management and therby improving the clinical outcome.There are several ways by which telemonitoring can be done. These are telephone based symptom monitoring, automated physiologic monitoring and automated monitoring of symptoms and signs. Trained nurses can collect the required information which can later be reviewed by physicians. In the automated systems the information regarding the symptoms, signs and physiological parameters are uploaded into the particular websites which are centrally located and monitored by heart failure specialists, cardiologists and or physicians.Heart failure in India has reached epidemic proportions. Early identification of the risk factors and initiation of appropriate therapy at early stages prevents development of heart failure. Clinical diagnosis and diagnostic imaging, echocardiogram in particular identifies patients with heart failure. The optimum utilization of the available drugs, general measures and surgical procedures appropriate to the condition improves the outcome of these patients.


MMeasurement of myocardial T1 mapping is possible with most of the clinically used magnets using sequences based on modification (MOLLI) or shortening (shMOLLI) of the Look-Locker (LL) sequence. However, the robustness of T1 post-processing approaches has not been systematically examined for these sequences, nor for different field strengths, in native and post-contrast T1 maps. Moreover, repeatability of measurements in conditions with altered geometric relations of cardiac chambers and wall thickness commonly observed in clinical settings remains unknown.2; n=11, 26). Fifteen subjects with normal CMR findings and low pretest likelihood served as controls . T1 maps were acquired in mid-ventricular short axis pre- and post-contrast using MOLLI, shMOLLI and LL sequences. Two independent observers drew ROIs conservatively within the septal and lateral myocardium, followed by semi-automatic propagation through the phases and manual correction for cardiac and respiratory motion  referred for clinical cardiac magnetic resonance (CMR). On the basis of CMR findings we created 3 groups with respective field strength  subgroups: increased LV wall thickness , and increased LV chamber . In contrast, lateral wall T1 time measurements showed considerably wider inter-observer variability (CoV=2.4-9). In addition, the CoVs were significantly higher in at 1.5T field strength, shMOLLI, and LL sequence (p<0.05). Regionally reduced signal-to noise ratio, sampling error from voxels straddling the myocardial-blood pool interface and measurement error in the lateral wall underlined the greater inter-observer variability in the lateral wall compared with the septum.We demonstrate that measurement of T1 values using conservative septal technique (CONSEPT) is robust and repeatable in healthy subjects and also in patients with significantly altered chamber relations. We propose the CONSEPT approach as the standardized post-processing method for T1 value derivation in clinical setting.National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award


Early and late microvascular obstruction (MVO) assessed by cardiovascular magnetic resonance (CMR) are prognostic markers for short-term clinical endpoints after acute ST-elevation myocardial infarction (STEMI). However, there is a lack of studies with long-term follow-up periods (>24 months).STEMI patients reperfused by primary angioplasty (n = 129) underwent MRI at a median of 2 days after the index event. Early MVO was determined on dynamic Gd first-pass images directly after the administration of 0.1 mmol/kg bodyweight Gd-based contrast agent. Furthermore, ejection fraction , left ventricular myocardial mass (LVMM) and total infarct size (% of LVMM) were determined with CMR. Clinical follow-up was conducted after a median of 52 months. The primary endpoint was defined as a composite of death, myocardial re-infarction, stroke, repeat revascularization, recurrence of ischemic symptoms, atrial fibrillation, congestive heart failure and hospitalization.vs. 15.5 g, p = 0.002) and a lower EF . The primary endpoint occurred in 66.2% of patients with MVO and in 42.4% of patients without MVO (p < 0.05). The presence of early MVO was associated with a reduced event-free survival (log-rank p < 0.05). Early MVO was identified as the strongest independent predictor for the occurrence of the primary endpoint in the multivariable Cox regression analysis adjusting for age, ejection fraction and infarct size .Follow-up was completed by 107 patients. 63 pre-defined events occurred during follow-up. Initially, 74 patients showed early MVO. Patients with early MVO had larger infarcts (mean: 24.9 g Early MVO, as assessed by first-pass CMR, is an independent long-term prognosticator for morbidity after AMI. Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) for acute ST-elevation myocardial infarction (STEMI) is a no reflow phenomenon in coronary vessels smaller than 200 μm despite adequate epicardial reperfusion . MicrovaClassical measures of MVO are the thromobolysis in myocardial infarction (TIMI) myocardial perfusion grade  and myocCardovascular magnetic resonance (CMR) with its concepts of first-pass perfusion and late-Gd-enhancement (LGE) imaging is a unique tool for investigating MVO -12. EarlThe morphological type of coronary lesion, a large vessel diameter and a high thrombus load have an impact on the occurrence of slow- or no-reflow phenomenon after primary angioplasty . FurtherDespite the increasing awareness of the clinical importance of MVO, there is a lack of long-term follow-up (>24 months) studies. Therefore, the aim of this study was to (a) assess clinical variables associated with early MVO and (b) evaluate the prognostic value of early MVO during a long-term follow-up (5 years).Patients reperfused by pPCI for STEMI at the University Hospital Innsbruck between 01/2005 and 12/2007 were asked to participate in the study. One-hundred and twenty-nine patients fulfilled inclusion criteria and gave their informed consent. The study was approved by the local ethics committee.Inclusion criteria were (a) diagnosis of ST-elevation myocardial infarction (STEMI) according to the redefined ESC/ACC committee criteria  as firstClinical follow-up was completed in 12/2010. The endpoints were defined by a consensus of the primarily involved investigators who were blinded to the CMR results. The primary endpoint was defined as a composite of death, myocardial re-infarction, stroke, repeat revascularization, recurrence of ischemic symptoms, atrial fibrillation, congestive heart failure and hospitalization of any cause. Secondary endpoints were defined as the individual endpoints of the composite primary endpoint.Ischemic symptoms were defined as the presence of typical anginal pain. Congestive heart failure was defined as episodes of cardiac decompensation, including edemas or worsening dyspnea of at least NYHA class III-IV requiring medical attention. If more than one end-point occurred in one patient the earliest and/or most severe end-point was chosen.th generation cTnT enzyme immunoassays  [CK activity was determined by an enzymatic assay  and cTnT concentrations were measured by 4Germany) .Blood samples for CK and cTnT measurements were collected routinely according to a standard protocol at least 3 times during the first 24 hours after admission and then daily. Maximum CK and cTnT levels as well as estimated cumulative CK and cTnT release were determined. Maximum cTnT and CK values served as an estimate of infarct size ,30.CMR was performed within at most 8 days after STEMI during hospitalization. All studies were performed on a 1.5 Tesla (T) MR scanner . The CMR protocol was described in detail previously   and end-systolic volume (ESV) as well as ejection fraction (EF) and myocardial mass (MM) were obtained from short axis cine-MR images, acquired using breath-hold, with retrospective ECG-triggered true-FISP. Evaluation was performed on standard software  by an experienced reader (G.K.) blinded to the clinical data.First-pass perfusion images were obtained in three short-axis sections centered on the mid-papillary muscle using an electrocardiograph-triggered T1-weighted inversion-recovery true-FISP sequence. A bolus injection of 0.1 mmol/kg body mass gadolinium contrast bolus  was administered by using an infusion pump  at 5 ml/sec . Sixty dvs. 3.3.16, TIANI Medgraph, Brunn am Gebirge, Austria); enhancement was defined using a threshold of +5 SD above the signal intensity of normal myocardium in the opposite myocardial segment [Ten min after a second intravenous gadolinium bolus injection of 0.1 mmol/kg body mass, LGE-CMR images were acquired by using an ECG-triggered phase-sensitive inversion-recovery (PSIR) single shot true-FISP sequence with consecutive short-axis slices as described in detail previously . The are segment -34. Furtχ2-test was used to compare categorical variables between groups. ANOVA with Bonferroni post-hoc testing (if ND) and Mann–Whitney U or Kruskal-Wallis test  were used to determine differences in continuous variables between groups. Pearson test was used for calculation of linear correlations for selected variables if they were ND. Otherwise, Spearman rank correlations were calculated. A p value p < 0.05 was considered to indicate statistical significance. Kaplan-Meier survival curves were determined and log-rank comparison was used between groups. Uni- and multivariate Cox-regression analysis was used to estimate hazard ratios (HR).For statistical analysis, the statistical software package SPSS 15.0  was used. All results for continuous variables are expressed as mean ± standard deviation (SD) or, if stated otherwise, as medians with corresponding interquartile range (IQR). Kolmogorov-Smirnov test was used to test for normal distribution (ND). Out of 129 patients, 5 patients (3.9%) did not complete the CMR due to claustrophobia, 124 patients underwent CMR scan within a median of 2 days (IQR: 2–4). Three (2.4%) scans were not diagnostic because of image quality. The remaining 121 patients were contacted after a median of 1613 days (IQR: 1374–1832 days). One-hundred and seven patients (88.4%) completed the follow-up. 11 (9.1%) patients were lost to follow-up, 3 (2.5%) patients could not be contacted for language reasons ; 99 patients (83.9%) were male, 19 (16.1%) were female. All patients underwent successful PCI of the culprit lesion with a median delay of 210 minutes (IQR: 120–330). 12 of them obtained additional prehospital fibrinolysis. For detailed patients characteristics, see Table vs. 45.5%, χ2: 3.88, p < 0.05) but did not differ from patients without early MVO (eMVO-) with regard to age, sex, body mass index (BMI) or the prevalence of the remaining cardiovascular risk factors . Furthermore, pain-to-balloon time, administration of prehospital lysis and mean pre- or post-interventional TIMI flow did not differ significantly between the groups .On initial CMR scans, 74 patients showed early MVO . eMVO + patients had a higher prevalence of hypertension , more transmural infarctions  and higher maximum biomarker levels  . Kaplan-Meier curves demonstrate a significantly reduced event-free survival times for eMVO + patients  compared to eMVO- patients  . Early MVO was associated with the occurrence of the primary endpoint when adjusting for age, ejection fraction and infarct size . Compared to age above median (=57 years), EF below median (=40.6%) and infarct size above median (=19.77 g) eMVO was the strongest independent predictor for the occurrence of the primary endpoint , congestive heart failure  and hospitalizations . The incidence of death, CV-death and myocardial re-infarction did not reach statistical significance.149 individual secondary endpoints occurred in patients with early MVO and 36 in patients without MVO. Table The primary results of this study are: (a) patients with early MVO had a higher prevalence of preexisting hypertension, but apart from that, showed similar risk profiles with regard to age, BMI, lipid status, smoking habits, diabetes and family history. (b) In line with most other MVO studies, a strong correlation between infarct size and early MVO was observed. (c) Early MVO is an independent long-term prognosticator of adverse clinical outcomes, especially recurrent ischemic symptoms, heart failure and repeat hospitalization, in a very long follow-up.MVO is an increasingly recognised phenomenon after pPCI for STEMI. Prevalence between 25% and 79% vs. 60 yrs [vs. 17% [Recently, two studies investigated predictors of late MVO defined by CMR, ECG and angiographic analysis ,35. Thei. 60 yrs  and 66 y. 60 yrs ) and the[vs. 17%  and 27% [vs. 17% ) can be vs. eMVO- 45.5%) which has, to the best of our knowledge, not been described previously. Data on the effects of hypertension on the cardiac microvasculature suggest impaired endothelial function in hypertensive subjects [et al. observed an inverse association of systolic blood pressure with the presence of MVO, which unfortunately we did not determine. The results of Husser et al. are explained by the authors as a result of a significant higher Killip class in patients with MVO and the resulting cardiogenic shock [In our study, the prevalence of hypertension was significantly higher in patients with eMVO  which was also not observed previously. In analogy with the explanation of Husser et al. that younger patients may lack ischemic preconditioning and coronary collaterals[There was a trend towards a lower number of active smokers among eMVO + patients , congestive heart failure  and hospitalisations of any kind . In line with these results, we observed a trend for a higher NYHA class at follow-up  as well as a trend for a higher number of cardiovascular hospitalisations  and atrial fibrillation .In our study, eMVO + patients differed from eMVO- patients in the occurrence of recurrent ischemic symptoms CMR, (late-Gd-enhanced) Cardiac magnetic resonance; cTnTmax, Maximum cardiac Troponin T; CV(D), Cardiovascular (disease); EDV, End-diastolic volume; ESV, End-systolic volume; (LV)EF, (left ventricular) Ejection fraction; PSIR-FISP, Phase-sensitive inversion-recovery fast-imaging-in-steady-state precession; IQR, Interquartile range; (LV)MM, (left ventricular) Myocardial mass; (e/l) MVO, (early/late) Microvascular obstruction; ND, Normally distributed; NYHA, New York heart association; pPCI, Primary percutaneous coronary interventions; ROC, Receiver operator characteristics; SD, Standard deviation; SV, Stroke volume; STEMI, ST-segment elevation myocardial infarction; TIMI, Thrombolysis in myocardial infarction.The authors declare that they have no competing interest.KG: Designed study. Collected, analysed and interpreted data. Statistical analysis. Wrote article. MA: Collected, analysed and interpreted CMR data. SS: Collected clinical data. ER: Collected CMR data. SM: Designed study. Statistical analysis. NM: Collected CMR data. JW: Revised the manuscript critically for intellectual content. PO: Revised the manuscript critically for intellectual content. MB: Study Coordinator. Designed study. Revised the manuscript critically for intellectual content. All authors read and approved the final manuscript.


Dual chamber pacing improves functional status and reduces left ventricular outflow tract gradients in some, but not all patients with hypertrophic cardiomyopathy (HCM) by altering ventricular depolarisation. We investigated the use of biventricular (BIV) pacing in symptomatic patients with HCM.8 patients aged 58±7yrs with symptomatic HCM underwent BIV pacing. 5 patients had LVOT gradients >30mmHg. Ventricular electrodes were placed in the right ventricle (RV) and a branch of the coronary sinus. An atrial electrode was inserted to achieve BIV pacing with a short AV delay. The short-term effects of different pacing modalities were assessed using 2-D and Doppler echocardiography. Symptoms and exercise tolerance were assessed after a month of each pacing mode. Long-term follow up data was available for 5 years.Baseline EF was 67±14% and mean QRS duration was 132±26msecs. BIV pacing reduced QRS duration compared to RV pacing . Five of the seven patients had baseline LVOT gradients (mean 67±25mmHg) that decreased to 41±15mm Hg with RV pacing (p<0.01) and 25±15mmHg with BIV pacing (p<0.005). Improvements in exercise time with active pacing occurred in six out of eight patients (75%), three (37.5%) had optimal exercise times with RV pacing and three with BIV pacing. Of the three patients with short term improvements with BIV pacing, one died 4 years post implant, one deteriorated with LV dilatation and one had the system explanted for infection.BIV pacing showed short-term beneficial effects in some patients over and above RV pacing alone. The mainstay of treatment for symptomatic patients with hypertrophic cardiomyopathy (HCM) is medical therapy, with surgical resection or alcohol septal ablation performed in patients with refractory symptoms and a significant left ventricular outflow tract (LVOT) gradient. Initial observational and uncontrolled studies reported benefits with dual chamber pacing with regard to symptoms and LVOT gradients -3. This The local research ethics committee approved the protocol and all patients gave written informed consent. Implants were performed over the period from January 2001 to January 2002.  In 3 patients an existing DDD pacing system was upgraded. An atrial electrode was positioned in the right atrial appendage and a right ventricular pacing lead  to the RV apex. A dedicated unipolar left heart pacing lead [Uni Aescula LV model 1055K-(Pacesetter-St Jude)] was placed to a branch of the coronary sinus from which adequate pacing and sensing of the LV could be performed. The RV lead was positioned as far as possible from the LV lead.  A DDDR pulse generator capable of simultaneously pacing both right and left ventricles was implanted in the left pectoral region. .Pacemakers were randomly programmed to either no active pacing (A) RV DDD pacing (B) or biventricular DDD pacing (C) in a serial crossover fashion. Patients were paced in modalities B and C at a rate of 70 beats/min with a short AV delay of 78 msecs for maximal ventricular pre-excitation. Patients were blinded to the pacing mode in an attempt to minimise placebo effect.Patients were evaluated in the short term after 4 weeks in each pacing modality. Objective exercise tolerance was assessed with  treadmilData are expressed as mean ±SD. Pacing parameters were analysed using ANOVA and post Hoc with Scheffes f test and a p value of < 0.05 was considered significant.  Statistical analysis was performed on an Apple Macintosh iBook Computer  using Statview 512+™ A BiV pacemaker was successfully implanted in 8 out of 9 patients.The mean age was 57±8 years and 75% were male. The mean QRS duration was 132±26ms, LVOT gradient 67±25 mmHg, ejection fraction (EF) 67±14% and average interventricular septal thickness was 2.0±0.6cm.Six patients (75%) had objective improvements in exercise capacity with RV or BIV pacing (responders) and two had no benefit or a reduced exercise capacity (non responders). Of the responders, 3 had better exercise capacity with BIV pacing (Group 1) and 3 with RV pacing (Group 2). Those that responded to BIV pacing compared to RV pacing tended to be more symptomatic , have have reduced exercise times , larger LVOT gradients  and a longer QRS duration  at baseline. Of the non responders, one patient had no objective improvement in exercise tolerance with either pacing modality despite a symptomatic improvement. Another had worsening of exercise tolerance with pacing despite a symptomatic improvement. This would suggest a significant placebo effect in these two patients.There was no significant difference between responders and non responders in terms baseline QRS duration  or exercise times , however there was a significant difference in baseline LVOT gradient .3 patients had maximal improvements in exercise time AND symptoms with BIV pacing.Baseline QRS was 145±20msecs, increasing to 211±50ms (p<0.05) with RV pacing and decreased to 133±50ms with BIV pacing. (p=ns) Baseline exercise time was 113±102 secs which was unchanged with RV pacing (105±65 secs) but increased to 205 ±137 secs with BIV pacing (p<0.05 vs. no and RV pacing). Symptoms scores progressively reduced (implying less symptoms) from 79±6 with no pacing to 69±15 with RV pacing to 35±16 with BIV pacing (p<0.05). Similarly there was a progressive fall in the LVOT gradients from 81±19mm Hg with no pacing to 48±17 with RV pacing and to 28±4 with BIV pacing .3 patients had better exercise tolerance with RV pacing compared to baseline and BIV pacing. Baseline QRS with no pacing was 120±36 msecs, 200±96 msecs with RV pacing and 121±33msecs with BIV pacing. Baseline exercise time was 352±120 secs increasing to 516±136 secs with RV pacing (p<0.05) and was 481±113 secs with BiV pacing. Despite better exercise times in this group with RV pacing, BIV pacing was associated with a further reduction in symptoms scores  and LVOT gradient (45±12mmHg at baseline decreasing to 30±4mmHg with RV pacing and 21±4mmHg with BIV pacing) when compared with RV pacing.Patients were left in the pacing mode, which showed greatest short-term benefit in terms of exercise times. Follow up is available on all patients 5 years since device implantation.Of the three patients that showed a short-term benefit with BIV pacing one patient died 43 months after their implant due to a gradual deterioration in LV function with end stage heart failure. One patient has deteriorated clinically and had entered the dilated phase of HCM. The third patient after an initial improvement deteriorated with development of atrial arrhythmias and needed explantation of the system due to pacemaker system infection and currently has a single chamber pacemaker.All 3 patients that were responders to RV pacing remained well. Two have had their pacemakers upgraded to ICDs. One at 36 months for non-sustained VT and one at 82 months post implant due to syncope, non-sustained ventricular tachycardia (NSVT) and a positive family history for sudden cardiac death.Of the non-responders, one patient developed NSVT with syncope. At that time is was not possible to individually switch off the LV lead, therefore the lead was extracted and upgraded to a dual chamber ICD 3 months following implantation. No further VT was documented following this during the 5 year follow up. The other patient died of progressive heart failure 36 months post implant.This is the first case series looking at the short term and long term effects of biventricular pacing in symptomatic patients with hypertrophic cardiomyopathy. In this small series there appeared to be a beneficial short term effect with pacing on exercise times, symptoms and outflow tract gradients in some but not all highly symptomatic patients. Of those with objective short term benefit, 50% appeared to have an incremental benefit from BIV pacing associated with a dramatic reduction in left ventricular outflow tract gradients. The mechanism of benefit from biventricular pacing in this small group of patients is unclear. Part of its beneficial effect could be related to alteration of the left ventricular contraction pattern. Simultaneous activation of the right and left posterolateral wall (the site of the LV pacing lead) would cause earlier apical contraction and later activation of the basal septum which could result in a decrease in the LVOT gradient. Those benefiting from BIV pacing had more severe exercise limitation, worse symptoms and larger outflow tract gradients. BIV pacing appeared to have an incremental effect on LVOT gradients over RV pacing alone. In one patient implanted with a device capable of independently altering VV timings it was possible to alter the gradient depending on the relative timing of LV and RV activation with greatest gradient reduction when LV was paced 4 msecs prior to the RV, with earlier LV activation times being not as effective in reducing the gradient. Of the patients with short term improvements from BIV pacing, two developed progressive LV dysfunction. This may simply represent the natural history in these patients with the severe forms of HCM degenerating into the dilated phase of their disease, rather than an effect of BIV pacing.Other points of note are the fact that several of the patients subsequently had ICDs and in one patient there was the suggestion that LV pacing may have been arrhythmogenic with non-sustained VT developing, which improved after LV lead extraction.Dual chamber RV pacing was initially proposed as an alternative therapy for symptomatic patients with hypertrophic cardiomyopathy. Its beneficial effects were thought to be explained by alteration of LV depolarization and optimization of atrial contraction ,10. InitBiventricular pacing has been shown to be beneficial in symptomatic patients with heart failure, with a number of studies demonstrating improved morbidity, mortality and its effects on reverse remodeling -30. In vWe reported the first case of the beneficial effect of biventricular pacing in a symptomatic patient with hypertrophic cardiomyopathy, preserved LV systolic function and a significant LVOT gradient . We founThis is a small series of patients and thus it is difficult to generalise the results. The patients who appeared to show a short term benefit with BIV pacing were a highly symptomatic group with significant electrical dyssynchrony. There also appeared to be a placebo effect in some patients who were paced. No measure of mechanical dyssynchrony were made with tools such as Doppler tissue imaging and therefore it is unclear as to whether improvements with BIV pacing were related to improved mechanical synchronisation. Also as the majority of devices were unable to program independent VV timing it is unclear as to whether optimisation of such timings with echocardiography may have been able to provide further benefit.We have shown short-term objective improvements in a small sub group of patients with HCM with the use of BIV pacing. With longer term follow up this benefit does not appear to be sustained. These findings require further investigation in a larger patient population in a randomised manner in the current era of devices with independent V-V programming to ascertain a potential mechanism of benefit.Biventricular pacing could therefore become an attractive alternative for alcohol septal ablation or surgical ablation in symptomatic patient with hypertrophic cardiomyopathy, especially in subjects requiring an ICD.


The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated.This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups  and cardiac measurements were compared using Pearson’s rank correlation over the four different groups.With advanced age a slight but significant decrease in ESV  and EDV  were observed associated with a significant increase in left  and right  ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05).The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies. Cardiac structural and functional ventricular values are important prognostic parameters for predicting patient outcome and are therefore commonly assessed with various methods ,2 wherebHowever, the precise impact of aging on the ventricular function has remained controversial. Several studies involving different methods concluded that aging does not have any impact on LV function ,7, whereHowever, the impact of age on both LV and in particular right ventricular (RV) function as assessed by CMR has not been investigated in large study populations. The aim of the present study was to compare LV and RV dimensions and EF over consecutive age decades.This retrospective study enrolled patients who underwent CMR for assessment of myocardial function including those individuals who had normal function and no cardiac pathology. In addition, the following exclusion criteria were applied: history of any cardiac disease, LV-EF <50% and/or RV-EF <45%, and EDV >235 ml  and >174 ml  as assessed by CMR . As a reSupine cardiac magnetic resonance imaging was performed using a 1.5 Tesla magnetic resonance (MR) scanner  using electrocardiogram (ECG) triggered breath-hold fast field echo acquisition imaging covering the heart from the valve plane to the apex with a slice thickness of 8 mm with no gap. The field of view was 450 × 400 × 96 mm. Sequence parameters included plane pixel size of 2.1 × 1.8 mm, acquisition time of 25 heart beats, flip angle of 60°, and repetition time/echo time of 3.4/1.7 ms. A cardiac synergy coil was used for signal acquisition and cardiac synchronization was performed with a vector ECG. Standard projections  were obtained for functional and structural assessment. Quantification of left and right ventricular values was performed using a dedicated software and workstation  by two independent CMR observers. In brief, LV and RV endocardial border were delineated in end-systolic and end-diastolic phases in all planes and EDV/ESV were calculated. LV mass was determined from the end-diastolic frames.Quantitative variables were expressed as mean ± standard deviation (SD) and categorical variables as frequencies or percentages. SPSS 20  was used for all statistical analysis. The Pearson’s correlation analysis was used to determine a correlation between the parameters of interest. P-values of less than 0.05 were considered statistically significant.This study included 183 subjects with functional and structural assessment of LV parameters. The quantitative RV parameters were available in 111 patients and the LV mass in 147 patients. The mean age of the study population was 52±14.7 years. The mean LV-EF was 64±7.0% while the mean RV-EF was 59±6.6%  whereas LV-ESV , LV-EDV , and LV myocardial mass  decreased significantly at advanced age  whereas RV-ESV  and RV-EDV  significantly decreased with increasing age (Figure The results in the different age groups are summarized in Table The present CMR study documents that increasing age is associated with a significant decrease in LV and RV volumes but an increase in EF. Furthermore, LV myocardial mass significantly decreased over the four age groups. There is increasing awareness on the fact that changes in cardiac ventricular structure and function attributable to the aging process may play an important role in modulating the cardiovascular response to disease . The knoDifferences in myocyte loss on the one hand and trophic effects on the other hand may eventually shift the tip of the balance towards changes in EF in the aging process. The observed decline in ventricular dimensions seems to favourably counterbalance the decrease in LV muscle mass resulting in an increase in EF. This is supported by the observation that twisting and torsion of the left ventricle are more pronounced in the elderly population  and it mWe acknowledge the following potential study limitations: First, in line with the data mentioned above we present a cross-sectional study of individuals at various ages, whereas patients would need to be followed in time to be more conclusive about age-related changes in cardiac parameters. Second, we did not verify our data with values obtained from another imaging modality and thus are not able to exclude potential modality bias. However, CMR is a well-accepted gold standard itself for such measurements . Third, In conclusion, the aging process has significant impact on ventricular EF, ESV and EDV in healthy CMR patients with normal functional and structural cardiac values. These findings underline the importance of using age adapted values as standard of reference in CMR studies.The authors have no competing interests to declare.MF, TAF and PAK were substantially involved in conceptual design of the study, statistical analysis of the data and drafting of the manuscript. CG, JS, BK, and BS were involved in critical review of data integrity, and gave their intellectual input concerning manuscript drafting. RM, CM, TAF and MF were substantially involved in acquisition of imaging data in daily clinical routine. Further, RM and CM gave substantial technical input regarding cardiac magnetic resonance imaging. FT, OG, and PAK critically reviewed the manuscript and gave important intellectual input. All authors have critically reviewed and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2342/13/6/prepub