Long-term follow-up of cardiac resynchronization therapy: mechanical resynchronization and reverse left ventricular remodeling are predictive for long-term transplant-free survival.

We sought to determine whether correction of mechanical left ventricular (LV) dyssynchrony as defined by tissue Doppler imaging (TDI) is predictive for transplant-free long-term survival in patients (pts.) undergoing cardiac resynchronization therapy (CRT). In 76 CRT recipients TDI curves from the septal, lateral, anterior, and inferior basal LV were obtained at baseline and after 6 ± 4 months. A time difference between regional electromechanical delays (EMD) of ≥40 ms was considered dyssynchronous. At follow-up, pts. were classified as TDI-responders (TDI-R: dyssynchrony at baseline, corrected by CRT) versus non-responders (TDI-NR: either not dyssynchronous at baseline, or persisting dyssynchrony). Pts. were then followed by standard echocardiography over 21 ± 6 months and were re-classified as LV remodelers (LV-R: LV volume reduction of >10%) versus non-remodelers (LV-NR). The end-point during clinical long-term follow-up of 65 ± 38 months was all-cause mortality or heart transplantation. 44 out of the 76 pts. (58%) were classified as TDI-R, 32 (42%) as TDI-NR. Significant reverse LV remodeling was observed in 41 (54%) pts., while 35 (46%) did not improve LV size and function. TDI-R was associated with LV-R in 35 pts. (85%; P < 0.001). During long-term follow-up, 38 pts. (50%) reached the end point, 11 (30%) in the TDI-R group, and 27 (70%) in the TDI-NR group (P < 0.0003). Mechanical resynchronization as defined by TDI translates into a significant survival benefit in CRT recipients.

Left atrial size and left ventricular hypertrophy correlate with myocardial fibrosis in patients with hypertrophic cardiomyopathy.

INTRODUCTION: In hypertrophic cardiomyopathy (HCM) risk assessment with respect to sudden cardiac death (SCD) is currently based on the presence or absence of different risk markers (RM). Recently, myocardial fibrosis as detected by gadolinium-enhanced magnetic resonance imaging (GE-MRI) has been suggested as additional RM. We evaluated the prevalence of myocardial fibrosis and examined correlations with other risk markers in patients considered to be at increased risk. METHODS: We included 50 patients with HCM with > 1 (2-4) RM who underwent GE-MRI to check for myocardial fibrosis. Late enhancement was assessed semi-quantitatively using a 17-segment model of the LV (from 0 = absent, 1 = point-shaped, 2 = limited to 1 LV segment, 3 = involving > or = 2 segments). Outflow obstruction was present in 25 patients, the other 25 (1 after septal ablation and after myectomy) were non-obstructive. RESULTS: Patients (33 men; mean age 44 +/- 13 years; NYHA class: 2.0 +/- 0.9) had a number of RM of 1.7 +/- 0.8. Evidence of myocardial fibrosis > or = 2 was found in 39 patients (mean score: 2.3 +/- 0.9). Correlations were found between left atrial diameter (eta = 0.5), septum thickness (eta = 0.6), and severity of fibrosis. Patients with fibrosis 2 had larger left atria (50 +/- 7 vs 43 +/- 7 mm, P = 0.007) and a thicker septum both on echocardiography (25 +/- 6 vs 17 +/- 5 mm, P < 0.001) and on GE-MRI (28 +/- 5 vs 20 +/- 4 mm, P = 0.01). No correlations were found between fibrosis score and other RM, global LV mass on GE-MRI, or other clinical variables. CONCLUSIONS: Left ventricular hypertrophy and left atrial size, as two markers for global disease severity, correlate with the severity of fibrosis on GE-MRI.

The diagnosis and treatment of hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common hereditary disease of the heart. METHODS: In this article, we summarize the current state of the diagnosis and treatment of HCM on the basis of a selective review of recent publications with relevance to clinical practice. RESULTS: Several hundred mutations in more than 27 genes, most of which encode sarcomeric structures, are associated with the HCM phenotype. Thus, HCM can be thought of as a sarcomeric disease, with myocardial fiber disarray as its histological hallmark. There are two types of HCM, a more common, obstructive type (HOCM, 70%) and a less common, non-obstructive type (HNCM; in all cases of HCM, testing should be performed to detect outflow obstruction at rest and/or on provocation, and to thereby determine whether HOCM or HNCM is present. The symptoms of HCM include dyspnea, angina pectoris, palpitations, dizziness, and occasionally syncope. Because sudden cardiac death is the most serious complication of HCM, particularly in young and asymptomatic patients, it follows that correct diagnosis, followed by risk stratification of patients with regard to the need for prophylactic implantation of an implantable cardiac defibrillator (ICD), can be of life-saving importance. The pharmacotherapy of symptomatic HNCM consists of the treatment of heart failure with a normal ejection fraction (HFNEF). In HOCM, the patient's symptoms and the obstructive gradient are the guide to treatment with beta-blockers or verapamil. For patients with drug-resistant disease, surgical myectomy and percutaneous septal ablation are now standard treatments. CONCLUSION: A near-normal life expectancy and a highly satisfactory quality of life are now realistic treatment goals for patients with HCM.

Peak systolic longitudinal strain of the lateral left ventricular wall improves after septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: a follow-up study using speckle tracking echocardiography.

Speckle tracking echocardiography (STE) or two-dimensional (2D) strain imaging is a novel ultrasound method to assess myocardial deformation. Peak systolic longitudinal strain (PSLS) of the basal septum (IVS) and the opposite lateral (LVFW) wall were measured in addition to standard echocardiography in 88 consecutive patients (pts) with obstructive hypertrophic cardiomyopathy (HOCM) who underwent a septal ablation procedure (PTSMA) and who were re-evaluated 12 ± 12 after months. At baseline, PSLS was substantially reduced both in basal regions. While PSLS remained unchanged in the basal IVS, i.e. the target region for PTSMA (baseline: -5.3 ± 4.1%; follow-up: -6.0 ± 4.3%; P=0.06), it improved in the opposite LVFW (from -9.4 ± 4.7 to -12.4 ± 4.8%; P<0.0001). Wall thickness decreased in both regions (Septum: from 20 ± 4 to 17 ± 4 mm; P<0.0001; LV free wall: from 13 ± 2 to 12 ± 2 mm; P=0.001). PSLS correlated significantly with wall thickness, both at baseline and at follow-up. NYHA functional class (from 2.9 ± 0.4 to 1.6 ± 0.6; P<0.0001) and objective exercise capacity (from 96 ± 42 to 114 ± 42 W; P=0.001) improved together with the reduction of outflow obstruction (LVOTO: from 62 ± 30 to 11 ± 19 mm Hg at rest, from 121 ± 26 to 43 ± 40 mm Hg with provocation; P<0.0001). During the 12 months of observation, no patient had a severe adverse event. Regional myocardial deformation can be assessed quantitatively by STE. Reduction of LV afterload by elimination of the outflow gradient following a successful PTSMA with low doses of alcohol results in improvement of systolic lateral longitudinal function.

Incidence of adequate ICD interventions in patients with hypertrophic cardiomyopathy supposed to be at high risk for sudden cardiac death.

INTRODUCTION: Although the incidence of sudden cardiac death (SCD) is as low as 1%/year in un-selected patients (pts) with hypertrophic cardiomyopathy (HCM), higher-risk populations may benefit from prophylactic implantation of an ICD. Risk assessment in HCM is thus important and currently based on the presence or absence of different risk markers (RM). STUDY AIM: The objective of this study is to correlate the incidence of adequate ICD interventions in HCM with the presence of different RM. METHODS: Fifty pts with HCM had ICD implantation, either for secondary (n = 2/4%), or primary prophylaxis of SCD (n = 48/96%). ICD for primary prophylaxis pts had more than 1 (2-4) RM. Outflow obstruction was present in 25 pts, the other 25, including I patient each after septal ablation and myectomy, were non-obstructive. ICD memories were read out and interpreted in accordance with established guidelines. RESULTS: The number of RM per patient was 1.7 +/- 0.8. During follow-up of 2.0 +/- 0.5 [0.2-6.3] years, adequate ICD interventions (11 episodes) were documented in 5, inadequate ICD interventions in 3 pts.Thirteen pts had at least I episode of atrial fibrillation. Pts with versus without events had a longer follow-up (3.2 +/- 4.3 vs. 1.8 +/- 2.6 years, P < 0.05), and were more frequently nonobstructive (all 5; P = 0.05).Within the time period observed no single RM was predictive for arrhythmic events. CONCLUSIONS: Incidence of appropriate ICD discharges was 4-5%/patient-year, supporting the proposed risk stratification. No single RM was predictive for future arrhythmic events.

Extracorporeal cardiac shock wave therapy ameliorates clinical symptoms and improves regional myocardial blood flow in a patient with severe coronary artery disease and refractory angina.

Different therapeutic options are being used for chronic coronary artery disease (CAD). We report about a 51-year-old female with CAD and refractory angina pectoris despite maximally tolerated medical therapy and after both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The patient received cardiac shock wave therapy (CSWT) over a period of 6 month. There was no arrhythmia during or after treatment; enzyme levels were normal at all times. PET imaging showed a substantial improvement of myocardial stress perfusion. Since the patient reported that she now was fully capable to deal with her everyday life, further treatment options were postponed. Our case report suggests that ultrasound-guided CSWT is able to improve symptoms and perfusion in ischemic myocardium.

Sleep-disordered breathing in heart failure with normal left ventricular ejection fraction.

AIMS: In patients with systolic heart failure (SHF) a high prevalence of sleep-disordered breathing (SDB) has been documented. The purpose of this study was to investigate the prevalence and type of SDB in patients with heart failure with normal left ventricular ejection fraction (HFNEF). METHODS AND RESULTS: Two hundred and forty-four consecutive patients (87 women, aged 65.3 +/- 1.4 years) with HFNEF underwent capillary blood gas analysis, measurement of NT-proBNP concentrations, echocardiography, cardiopulmonary exercise testing (CPX), cardiorespiratory polygraphy, and simultaneous right and left heart catheterization. Sleep-disordered breathing was defined as an apnoea-hypopnoea-index (AHI) > or = 5/h. Sleep-disordered breathing was documented in 69.3% of all patients, 97 patients (39.8%) presented with OSA and 72 patients (29.5%) with CSA. With an increasing impairment of diastolic function the proportion of SDB, and CSA in particular, increased. Patients with SDB performed worse on CPX and six-minute walk test. Partial pressure of CO(2) was lower in CSA, whereas AHI, left atrial diameter, NT-proBNP, LVEDP, PAP, and PCWP were higher. CONCLUSION: There is a high prevalence of SDB in HFNEF. In parallel to SHF, CSA patients in particular are characterized by a more impaired cardiopulmonary function. Whether SDB is of prognostic relevance in HFNEF needs to be determined.

Percutaneous septal ablation after unsuccessful surgical myectomy for patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVE: To evaluate the long-term outcome of percutaneous septal ablation (PTSMA) after a previous myectomy. BACKGROUND: Myectomy usually results in symptomatic improvement and reduction of dynamic obstruction in hypertrophic obstructive cardiomyopathy patients (HOCM-pts.). However, a few pts. remain with severe symptoms and obstruction, and need additional interventions. METHODS: We reviewed our database of 450 pts. who underwent PTSMA in our institution, and identified 11 (7 women, 4 men, mean age: 50 +/- 14 years) with residual or recurrent NYHA class symptoms > or =III and significant left ventricular outflow obstruction (LVOTO) despite a previous myectomy 4 +/- 5 years ago. In-hospital and follow-up data covering 6 +/- 4 years, focusing on mortality and morbidity, symptoms, exercise capacity, and echocardiographic measures were collected. RESULTS: PTSMA was performed by injection of 3.6 +/- 2.9 ml of alcohol. There was no peri-procedural or late death in this cohort. CK peaked at 614 +/- 434 U/l. In addition to two pts. who already had a pacemaker implanted, two more (18%) who both had pre-existing left bundle branch block were pacemaker-dependent after PTSMA. During follow-up, 9 pts. (81%) reported significant and stable improvement. Two pts. (18%) developed progressive class III symptoms until their last follow-up, one of these together with persistent AF and a non-fatal stroke, the other received an ICD for primary prophylaxis and entered our pre-transplant program. Echo-Doppler showed sustained LVOTO elimination without global LV dilatation in all cases. CONCLUSIONS: PTSMA is an effective non-surgical option for treating symptoms and residual or recurrent LVOTO after a previous surgical myectomy. The high rate of conduction disturbances in this post-surgical cohort translated into a higher rate of pacemaker dependency after PTSMA.

Etiology of stroke after mechanical heart valve replacement--results from a ten-year prospective study.

BACKGROUND AND AIMS OF THE STUDY: In patients carrying mechanical valve prostheses it is assumed that cardioembolic strokes account for 70 - 90 % of clinically diagnosed thromboembolic complications. The etiology of stroke especially in older patients with mechanical heart valves may thus be multiple and not prosthetic valve-related in a substantial percentage. It was the aim of this prospective study to analyze the etiology of stroke in consecutive patients, who had mechanical heart valve replacement before. METHODS: During a 10-year period, 89 consecutive patients were hospitalized at the authors' institution late (> 90 days) after mechanical valve replacement with definite stroke according to the WHO Monica criteria for stroke registers. RESULTS: CCT or MRI revealed cerebral bleedings in 69 (77.5 %) patients, which were small in 42 (60.9 %), intermediate in 24 (34.8 %), and massive in three (4.3 %). Non-embolic, lacunary infarctions were documented in seven (8 %) and embolic strokes in 13 (17%) patients. According to the findings by CCT/ MRI and duplex sonography of the carotid arteries, stroke was considered atherothrombotic in seven of these 13 patients with embolic strokes (53.8 %). Six of these seven patients (86 %) had recurrent neurologic symptoms. In the other four, prosthesis-related stroke was most likely due to a yet undiagnosed active prosthetic valve endocarditis. In only two (2.3%) of the 89 stroke patients, was etiology probably prosthesis-related. Patients with an INR > 5.0 had ischemic stroke in three, and bleedings in four, patients with an INR < 1.8 ischemic strokes in one, and bleedings in three cases. CONCLUSIONS: In conclusion, the vast majority of strokes after mechanical valve implantation in our cohort study were hemorrhagic rather than ischemic in origin, irrespective of the intensity of the oral anticoagulation. For proper treatment decisions, it is therefore essential to discriminate the underlying etiology of stroke.

Influence of two different reporting systems on counts of thromboembolic and bleeding complications after St. Jude medical valve replacement: results from the GELIA study.

BACKGROUND AND AIM OF THE STUDY: Different standards for the reporting of morbid events and different follow up techniques have a profound impact on reported morbidity after prosthetic valve replacement. Most studies follow the guidelines of The American Association of Thoracic Surgery (AATS) and The Society of Thoracic Surgeons (STS); the present authors' group has now developed an adapted Karnofsky scale which allows a more precise grading of the severity of morbid events. METHODS: The AATS/STS criteria and the adapted Karnofsky criteria were applied to the database of the German Experience with Low-Intensity Anticoagulation (GELIA) study. In a study population of 2,735 patients, GELIA compared three different intensities of oral anticoagulation in a prospective and randomized design. Patients registered morbid events prospectively by means of documentation cards. RESULTS: The overall rate of complications was comparable when utilizing the two classification systems. However, use of the AATS/STS criteria resulted in the counting of fewer bleeding complications, because only major bleedings were recorded. In contrast, the incidence of embolic complications was higher compared to the Karnofsky criteria because all events were counted, irrespective of their severity, while clinically insignificant (transient, reversible within 24 h) events were disregarded when using the Karnofsky grading. CONCLUSION: The adapted Karnofsky criteria provide a precise and easily understandable framework for the assessment of complications, with equal weighting of both hemorrhagic and embolic events.

Drug insight: an overview of current anticoagulation therapy after heart valve replacement.

Vitamin K antagonists, such as warfarin, are the gold standard approach for the long-term anticoagulant therapy of patients with mechanical heart valves. Management decisions are, however, based predominantly on expert consensus and on data from nonrandomized, follow-up studies, which have inherent limitations in their methods. Low-intensity anticoagulation therapy provides protection against thromboembolic complications in patients with most types of modern prosthetic heart valve. The addition of low-dose aspirin is safe if international normalized ratio values below 3.5 are maintained. A combined regimen should be considered in high-risk patients and those with coexistent coronary artery or cerebrovascular disease, and in patients who have suffered a thromboembolic event despite a therapeutic international normalized ratio. Thromboprophylaxis with unfractionated or low-molecular-weight heparins is restricted to specific situations, such as when a patient is intolerant to vitamin K antagonists, when surgical procedures require discontinuation of oral anticoagulation, or when the patient is pregnant. A lack of uniformity across practice guidelines make it difficult to reach treatment decisions. Each patient's preference, expressed after counseling about the risks and benefits of each treatment strategy, and an individual assessment of the patient's risk factors, should guide treatment decisions. At present, new anticoagulant agents such as factor Xa inhibitors do not represent a treatment option for heart valve recipients.

Thromboembolic and bleeding complications following St. Jude Medical valve replacement: results of the German Experience With Low-Intensity Anticoagulation Study.

STUDY OBJECTIVES: Due to their inherent thrombogenicity, mechanical cardiac valves necessitate lifelong oral anticoagulation. Less intensive oral anticoagulation than recommended earlier might result in a lower incidence of bleeding complications without increasing the embolic hazard significantly. DESIGN: Comparison of three different intensities of oral anticoagulation in a prospective, randomized multicenter design. Three months after valve replacement, patients were randomly assigned to stratum A, international normalized ratio (INR) 3.0 to 4.5; stratum B, INR 2.5 to 4.0; or stratum C, INR 2.0 to 3.5. PATIENTS: Data from 2,735 patients following aortic valve replacement (AVR; n = 2,024), mitral valve replacement (MVR; n = 553), and combined AVR and MVR (n = 158) with the St. Jude Medical (SJM) valve (St. Jude Medical; St. Paul, MN) between July 1993 and May 1999 were analyzed, covering a total follow-up period of 6,801 patient-years. All complications were registered prospectively. MEASUREMENTS AND RESULTS: Fifty-one thromboembolic events (TEs) were documented, resulting in a linearized incidence of 0.75 TEs per 100 patient-years, 22 of which were minor (0.32% per patient-year), 10 were moderate (0.15% per patient-year), and 19 were severe (0.28% per patient-year). Thromboembolism following AVR was significantly lower than after MVR (0.53% per patient-year vs 1.64% per patient-year). Patients reported 1,687 bleeding complications (24.8% per patient-year). The vast majority of bleeding complications (n = 1,509; 22.2% per patient-year) were classified as minor, 140 were classified as moderate (2.06% per patient-year), and 38 were classified as severe (0.56% per patient-year). The clinically relevant incidences of moderate and severe TEs and bleeding complications were not significantly different between the three prespecified INR strata. CONCLUSIONS: The intention-to-treat analysis of the results of the German Experience With Low Intensity Anticoagulation study leads to the unexpected result that despite a sophisticated reporting system, the incidence of moderate and severe TE and bleeding complications was comparably low in all INR strata and more or less within the so-called background incidence reported for an age-related "normal" population. This study supports reexamination of the intensity of anticoagulation in patients with the SJM valve.

Quantitative analysis of intraprocedural myocardial contrast echocardiography during percutaneous septal ablation for hypertrophic obstructive cardiomyopathy.

AIMS: We tested whether procedural success of percutaneous septal ablation for hypertrophic obstructive cardiomyopathy is related to quantitative measurements of intraprocedural myocardial contrast echocardiography. METHODS AND RESULTS: In a study group of 34 patients, the mean area of the contrast depot was 8.5+/-2.5 cm2, its length along the left ventricular endocardial border 3.0+/-0.7 cm and its proximal edge 2.0+/-0.6 cm upstream the point of mitral-septal contact. Clinical and hemodynamic success was achieved in all but one patient 3 months following percutaneous septal ablation. The proximal edge of the ablation lesion correlated weakly (r=0.5) with the proximal edge of the contrast depot with respect to their distance from the mitral valve leaflet tips. No other correlations were found between the efficacy of percutaneous septal ablation and various quantitative measurements of intraprocedural contrast echocardiography. CONCLUSIONS: The localization of the ablation lesion 3 months after percutaneous septal ablation is predicted by the localization of the contrast depot with respect to the point of mitral-septal contact. The final hemodynamic effect of the ablation lesion, however, does not correlate with quantitative parameters of intraprocedural contrast echocardiography, but appears to be the result of an individual remodeling process.

Influence of atypical symptoms and electrocardiographic signs of left ventricular hypertrophy or ST-segment/T-wave abnormalities on the natural history of otherwise asymptomatic adults with moderate to severe aortic stenosis: preliminary communication.

BACKGROUND AND AIM OF THE STUDY: Current guidelines recommend that aortic valve replacement (AVR) is deferred in asymptomatic patients with aortic stenosis until symptoms develop. Classical symptoms include exertional dyspnea, angina pectoris and syncope. The influence of atypical symptoms (dizziness, exertional intolerance, fatigue, palpitations/arrhythmias) and electrocardiographic signs of left ventricular hypertrophy or ST-segment/T-wave abnormalities on the natural course of the disease is unknown. METHODS: The clinical course of 100 patients with a preliminary diagnosis of asymptomatic aortic stenosis with respect to clinical signs and symptoms mentioned above was examined. All patients underwent serial echocardiographic examinations with calculation of aortic valve area by the continuity equation. RESULTS: Two patients died during a mean follow up period of 34 +/- 32 months (range: 1-116 months). There were no peri- or postoperative deaths. Seven patients with hemodynamically severe aortic stenosis and concomitant atrial fibrillation, four with classical symptoms after re-evaluation, and five with left ventricular dysfunction underwent short-term AVR and were excluded from any subsequent analysis. In total, 84 patients were either entirely asymptomatic (n = 57; group A) or had atypical symptoms (n = 27; group B). Of these patients, 18 underwent AVR before onset of classical symptoms for various reasons, and 21 were treated medically. The remaining 15 group B patients exhibited classical symptoms significantly earlier than the remaining 30 group A patients (15 +/- 7 versus 35 +/- 24 months; p < 0.002). Aortic valve area tended to decrease more rapidly in group B patients than in group A patients (-0.16 +/- 0.12 versus -0.11 +/- 0.07 cm2 per year; p = 0.053). Clinical and hemodynamic progression were further increased if additional electrocardiographic abnormalities were present. CONCLUSION: Both atypical symptoms and electrocardiographic signs of left ventricular hypertrophy/strain shorten the time interval until otherwise asymptomatic patients exhibit classical symptoms of advanced aortic stenosis requiring prosthetic valve replacement.