ABSTRACT
AIMS: The field of conduction system pacing (CSP) is evolving, and our aim was to obtain a contemporary picture of European CSP practice. METHODS AND RESULTS: A survey was devised by a European CSP Expert Group and sent electronically to cardiologists utilizing CSP. A total of 284 physicians were invited to contribute of which 171 physicians (60.2%; 85% electrophysiologists) responded. Most (77%) had experience with both His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Pacing indications ranked highest for CSP were atrioventricular block (irrespective of left ventricular ejection fraction) and when coronary sinus lead implantation failed. For patients with left bundle branch block (LBBB) and heart failure (HF), conventional biventricular pacing remained first-line treatment. For most indications, operators preferred LBBAP over HBP as a first-line approach. When HBP was attempted as an initial approach, reasons reported for transitioning to utilizing LBBAP were: (i) high threshold (reported as >2â V at 1â ms), (ii) failure to reverse bundle branch block, or (iii) > 30â min attempting to implant at His-bundle sites. Backup right ventricular lead use for HBP was low (median 20%) and predominated in pace-and-ablate scenarios. Twelve-lead electrocardiogram assessment was deemed highly important during follow-up. This, coupled with limitations from current capture management algorithms, limits remote monitoring for CSP patients. CONCLUSIONS: This survey provides a snapshot of CSP implementation in Europe. Currently, CSP is predominantly used for bradycardia indications. For HF patients with LBBB, most operators reserve CSP for biventricular implant failures. Left bundle branch area pacing ostensibly has practical advantages over HBP and is therefore preferred by many operators. Practical limitations remain, and large randomized clinical trial data are currently lacking.
Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Humans , Stroke Volume/physiology , Ventricular Function, Left , Treatment Outcome , Heart Conduction System , Bundle-Branch Block/diagnosis , Bundle-Branch Block/therapy , Arrhythmias, Cardiac/therapy , Heart Failure/diagnosis , Heart Failure/therapyABSTRACT
AIMS: Permanent transseptal left bundle branch area pacing (LBBAP) is a promising new pacing method for both bradyarrhythmia and heart failure indications. However, data regarding safety, feasibility and capture type are limited to relatively small, usually single centre studies. In this large multicentre international collaboration, outcomes of LBBAP were evaluated. METHODS AND RESULTS: This is a registry-based observational study that included patients in whom LBBAP device implantation was attempted at 14 European centres, for any indication. The study comprised 2533 patients (mean age 73.9 years, female 57.6%, heart failure 27.5%). LBBAP lead implantation success rate for bradyarrhythmia and heart failure indications was 92.4% and 82.2%, respectively. The learning curve was steepest for the initial 110 cases and plateaued after 250 cases. Independent predictors of LBBAP lead implantation failure were heart failure, broad baseline QRS and left ventricular end-diastolic diameter. The predominant LBBAP capture type was left bundle fascicular capture (69.5%), followed by left ventricular septal capture (21.5%) and proximal left bundle branch capture (9%). Capture threshold (0.77â V) and sensing (10.6â mV) were stable during mean follow-up of 6.4 months. The complication rate was 11.7%. Complications specific to the ventricular transseptal route of the pacing lead occurred in 209 patients (8.3%). CONCLUSIONS: LBBAP is feasible as a primary pacing technique for both bradyarrhythmia and heart failure indications. Success rate in heart failure patients and safety need to be improved. For wider use of LBBAP, randomized trials are necessary to assess clinical outcomes.
Subject(s)
Bundle of His , Heart Failure , Humans , Female , Aged , Cardiac Pacing, Artificial/adverse effects , Cardiac Pacing, Artificial/methods , Bundle-Branch Block/therapy , Bundle-Branch Block/etiology , Bradycardia/therapy , Bradycardia/etiology , Electrocardiography/methods , Treatment OutcomeABSTRACT
BACKGROUND: Early recognition of viable myocardium after acute myocardial infarction (AMI) is of clinical relevance, since affected segments have the potential of functional recovery. Delayed contrast-enhanced magnetic resonance imaging (DCE-CMR) has been validated extensively for the detection of viable myocardium. An alternative parameter for detecting viability is the perfusable tissue index (PTI), derived using [15O]H2O positron emission tomography (PET), which is inversely related to the extent of myocardial scar (non-perfusable tissue). The aim of the present study was to investigate the predictive value of PTI on recovery of LV function as compared to DCE-CMR in patients with AMI, after successful percutaneous coronary intervention (PCI). METHODS: Thirty-eight patients with ST elevation myocardial infarction (STEMI) successfully treated by PCI were prospectively recruited. Subjects were examined 1 week and 3 months (mean follow-up time: 97 ± 10 days) after AMI using [15O]H2O PET and DCE-CMR to assess PTI, regional function and scar. Viability was defined as recovery of systolic wall thickening ≥3.0 mm at follow-up by use of CMR. A total of 588 segments were available for serial analysis. RESULTS: At baseline, 180 segments were dysfunctional and exhibited DCE. Seventy-three (41%) of these dysfunctional segments showed full recovery during follow-up (viable), whereas 107 (59%) segments remained dysfunctional (nonviable). Baseline PTI of viable segments was 0.94 ± 0.09 and was significantly higher compared to nonviable segments (0.80 ± 0.13, P < .001). The optimal cut-off value for PTI was ≥0.85 with a sensitivity of 85% and specificity of 72%, and an area under the curve (AUC) of 0.82. In comparison, a cut-off value of <32% for the extent of DCE resulted in a sensitivity of 72% and a specificity of 69%, and an AUC of 0.75 (AUC PTI vs DCE P = .14). CONCLUSION: Assessment of myocardial viability shortly after reperfused AMI is feasible using PET. PET-derived PTI yields a good predictive value for the recovery of LV function in PCI-treated STEMI patients, in excellent agreement with DCE-CMR.
Subject(s)
Magnetic Resonance Imaging, Cine/methods , Myocardial Perfusion Imaging/methods , Myocardial Stunning/diagnostic imaging , Myocardial Stunning/etiology , Positron-Emission Tomography/methods , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/diagnostic imaging , Contrast Media , Early Diagnosis , Feasibility Studies , Female , Humans , Male , Middle Aged , Oxygen Radioisotopes , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , WaterABSTRACT
The most common manifestation of Lyme carditis is a varying degree of atrioventricular (AV) conduction block. This case describes a 45-year-old male with third-degree AV block due to Lyme carditis. Treatment with intravenous antibiotics resulted in complete normalization of AV conduction, thereby averting permanent pacemaker implantation.
Subject(s)
Atrioventricular Block/diagnosis , Atrioventricular Block/etiology , Lyme Disease/complications , Lyme Disease/diagnosis , Myocarditis/complications , Myocarditis/diagnosis , Anti-Bacterial Agents/therapeutic use , Atrioventricular Block/prevention & control , Diagnosis, Differential , Electrocardiography/methods , Humans , Lyme Disease/drug therapy , Male , Middle Aged , Myocarditis/drug therapy , Treatment OutcomeABSTRACT
Background: Conduction system pacing (CSP), either as His bundle pacing (HBP) or as left bundle branch area pacing (LBBAP), may be superior to right ventricular apical or septal pacing. Objective: The study sought to present acute results for a new guiding catheter (Biotronik Selectra 3D) designed for CSP implantations of a retractable screw-in lead (Biotronik Solia S). Methods: The primary endpoint of the prospective, international nonrandomized BIO|MASTER.Selectra 3D study was freedom from catheter-related serious adverse device effects (SADEs) within 1 week of lead implantation. Results: Of 157 enrolled patients, CSP was achieved in 147 (93.6%) patients. No SADEs occurred within 7 days. LBBAP was achieved in 82 patients (45 as crossover from an HBP attempt) and HBP in 65 (44.2%) patients. In centers considering both HBP and LBBAP, the CSP implantation success approached 99%. Successful CSP implantations lasted on average â¼50 minutes (fluoroscopy â¼6 minutes). Most procedures (87.9%) needed only 1 catheter, even after switch from HBP to LBBAP. The catheter's handling was rated largely positive. In patients without bundle branch block, mean QRS duration increased from 106 ms (intrinsic) to 122 ms (CSP) (P = .001). In patients with bundle branch block, mean QRS duration decreased from 151 ms (intrinsic) to 137 ms (CSP) (P = .004). Conclusion: The Selectra 3D catheter is a valuable tool for HBP and LBBAP implantations of the stylet-supported pacemaker leads. When implanters considered both HBP and LBBAP, the success rate was â¼99%. Flexibility to change between different approaches may be advisable in heterogeneous and challenging areas, such as CSP implantations.
ABSTRACT
This study investigated the effects of alcohol septal ablation (ASA) on microcirculatory function and myocardial energetics in patients with hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract (LVOT) obstruction. In 15 HCM patients who underwent ASA, echocardiography was performed before and 6 mo after the procedure to assess the LVOT gradient (LVOTG). Additionally, [(15)O]water PET was performed to obtain resting myocardial blood flow (MBF) and coronary vasodilator reserve (CVR). Changes in LV mass (LVM) and volumes were assessed by cardiovascular magnetic resonance imaging. Myocardial oxygen consumption (MVo(2)) was evaluated by [(11)C]acetate PET in a subset of seven patients to calculate myocardial external efficiency (MEE). After ASA, peak LVOTG decreased from 41 ± 32 to 23 ± 19 mmHg (P = 0.04), as well as LVM (215 ± 74 to 169 ± 63 g; P < 0.001). MBF remained unchanged (0.94 ± 0.23 to 0.98 ± 0.15 ml·min(-1)·g(-1); P = 0.45), whereas CVR increased (2.55 ± 1.23 to 3.05 ± 1.24; P = 0.05). Preoperatively, the endo-to-epicardial MBF ratio was lower during hyperemia compared with rest (0.80 ± 0.18 vs. 1.18 ± 0.15; P < 0.001). After ASA, the endo-to-epicardial hyperemic (h)MBF ratio increased to 1.03 ± 0.26 (P = 0.02). ΔCVR was correlated to ΔLVOTG (r = -0.82; P < 0.001) and ΔLVM (r = -0.54; P = 0.04). MEE increased from 15 ± 6 to 20 ± 9% (P = 0.04). Coronary microvascular dysfunction in obstructive HCM is at least in part reversible by relief of LVOT obstruction. After ASA, hMBF and CVR increased predominantly in the subendocardium. The improvement in CVR was closely correlated to the absolute reduction in peak LVOTG, suggesting a pronounced effect of LV loading conditions on microvascular function of the subendocardium. Furthermore, ASA has favorable effects on myocardial energetics.
Subject(s)
Ablation Techniques , Cardiomyopathy, Hypertrophic/metabolism , Cardiomyopathy, Hypertrophic/surgery , Energy Metabolism/physiology , Ethanol , Heart Septum/surgery , Microcirculation/physiology , Myocardium/metabolism , Algorithms , Cardiomyopathy, Hypertrophic/diagnostic imaging , Coronary Circulation , Echocardiography , Endocardium/physiology , Female , Hemodynamics , Humans , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Middle Aged , Myocardial Contraction/physiology , Oxygen Consumption , Pericardium/physiology , Positron-Emission Tomography , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/metabolism , Ventricular Dysfunction, Left/surgery , Ventricular Function, LeftABSTRACT
Background In survivors of sudden cardiac arrest with obstructive coronary artery disease, it remains challenging to distinguish ischemia as a reversible cause from irreversible scar-related ventricular arrhythmias. We aimed to evaluate the value of implantable cardioverter-defibrillator (ICD) implantation in sudden cardiac arrest survivors with presumably reversible ischemia and complete revascularization. Methods and Results This multicenter retrospective cohort study included 276 patients (80% men, age 67±10 years) receiving ICD implantation for secondary prevention. Angiography was performed before ICD implantation. A subgroup of 166 (60%) patients underwent cardiac magnetic resonance imaging with late gadolinium enhancement before implantation. Patients were divided in 2 groups, (1) ICD-per-guideline, including 228 patients with incomplete revascularization or left ventricular ejection fraction ≤35%, and (2) ICD-off-label, including 48 patients with complete revascularization and left ventricular ejection fraction >35%. The primary outcome was time to appropriate device therapy (ADT). During 4.0 years (interquartile range, 3.5-4.6) of follow-up, ADT developed in 15% of the ICD-off-label group versus 43% of the ICD-per-guideline group. Time to ADT was comparable in the ICD-off-label and ICD-per-guideline groups (hazard ratio (HR), 0.46; P=0.08). No difference in mortality was observed (HR, 0.95; P=0.93). Independent predictors of ADT included age (HR, 1.03; P=0.01), left ventricular end-diastolic volume HR, (1.05 per 10 mL increase; P<0.01) and extent of transmural late gadolinium enhancement (HR, 1.12; P=0.04). Conclusions This study demonstrates that sudden cardiac arrest survivors with coronary artery disease remain at high risk of recurrent ventricular arrhythmia, even after complete revascularization and with preserved left ventricular function. Late gadolinium enhancement-cardiac magnetic resonance imaging derived left ventricular volumes and extent of myocardial scar were independently associated with.
Subject(s)
Coronary Artery Disease/complications , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Myocardial Revascularization , Secondary Prevention/methods , Tachycardia, Ventricular/therapy , Aged , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging, Cine/methods , Male , Myocardium/pathology , Retrospective Studies , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Time FactorsABSTRACT
PURPOSE: Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO(2)), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). METHODS: Twenty patients with HCM (12 men, mean age: 55.2 + or - 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 + or - 10 years) were studied with [(11)C]acetate PET to assess MVO(2). CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. RESULTS: Between study groups, MVO(2) (controls: 0.12 + or - 0.04 ml x min(-1) x g(-1), HCM: 0.13 + or - 0.05 ml x min(-1) x g(-1), p = 0.64) and EW (controls: 9,139 + or - 2,484 mmHg x ml, HCM: 9,368 + or - 2,907 mmHg x ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 + or - 21 g, HCM: 200 + or - 76 g, p < 0.001) and MEE was decreased in HCM patients (controls: 35 + or - 8%, HCM: 21 + or - 10%, p < 0.001). MEE was related to stroke volume (SV), LV outflow tract gradient, NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) and serum free fatty acid levels (all p < 0.05). Multivariate analysis revealed that SV (ss = 0.74, p < 0.001) and LVM (ss = -0.43, p = 0.013) were independently related to MEE. CONCLUSION: HCM is characterized by unaltered MVO(2), impaired EW generation per gram of myocardial tissue and subsequent deteriorated myocardial efficiency. Mechanical external efficiency could independently be predicted by SV and LVM.
Subject(s)
Cardiomyopathy, Hypertrophic/metabolism , Heart/diagnostic imaging , Magnetic Resonance Imaging , Myocardium/metabolism , Positron-Emission Tomography , Adult , Aged , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/pathology , Echocardiography, Doppler, Pulsed , Female , Humans , Male , Middle Aged , Mitral Valve/physiopathology , Myocardial Contraction , Myocardium/pathology , Oxygen Consumption , Ventricular Outflow Obstruction/physiopathologyABSTRACT
Besides stimulating erythropoiesis, erythropoietin (EPO) exerts powerful proangiogenic and antiapoptotic effects. These erythropoiesis-independent effects are potentially useful as a supplement for the treatment of chronic heart failure (CHF). EPO may improve microvascular capacity of ischemic myocardial tissue and could thereby (partially) restore myocardial function. In addition, EPO could protect cardiomyocytes from hypoxic damage and prevent them from apoptosis. However, the clinical value of these erythropoiesis-independent effects for the treatment of CHF remains to be elucidated. Small-sized trials evaluating the effects of EPO treatment on surrogate endpoints in patients with CHF showed positive effects in general; however, their mutual results are not always unambiguous. Moreover, increasing hematocrit levels with EPO has been associated with increased blood viscosity and an inherent risk of thromboembolic events. A currently running multicenter phase III trial is designed to provide clarity concerning the effects of EPO on outcome and safety in patients with CHF. Focusing primarily on outcome, however, does not provide insight into the mode of action and isolated benefits of the erythropoiesis-independent effects of EPO. Further exploration of these effects is a key issue to gain knowledge of the full potential of EPO for the treatment of CHF.
Subject(s)
Anemia/physiopathology , Apoptosis/physiology , Erythropoietin/physiology , Heart Failure/physiopathology , Myocardial Reperfusion , Anemia/drug therapy , Animals , Apoptosis/drug effects , Chronic Disease , Erythropoietin/therapeutic use , Heart Failure/drug therapy , Humans , Myocardial Reperfusion/methodsABSTRACT
Recommendations for prophylactic implantable cardioverter defibrillator (ICD) implantation in asymptomatic heart failure patients with a reduced left ventricular ejection fraction (LVEF) differ between guidelines. Evidence on the risk of appropriate device therapy (ADT) and death in New York Heart Association (NYHA) class I patients is scarce. Aim of this study is to evaluate ADT and mortality in NYHA-I primary prevention ICD patients with a LVEF ≤35%. A retrospective cohort was studied, including 572 patients with LVEF ≤35% who received a prophylactic ICD with or without resynchronization therapy (CRT-D). To evaluate the incidence of ADT and mortality, NYHA-I was compared with NYHA-II-III using Cox regression analysis. During a follow-up of 4.1 ± 2.4 years, 33% of the NYHA-I patients received ADT compared with 20% of the NYHA-II-III patients (hazard ratio 1.5, 95% confidence interval 1.04 to 2.31, pâ¯=â¯0.03). No differences in mortality were observed (hazard ratio 0.70, 95% confidence interval 0.49 to 1.07, pâ¯=â¯0.10). Additional analyses showed no difference in time to ADT excluding CRT patients (ICD-NYHA-I patients vs ICD-NYHA-II-III patients, pâ¯=â¯0.17) and comparing ischemic and nonischemic cardiomyopathy NYHA-I patients (pâ¯=â¯0.13). Multivariable Cox regression analyses showed that NYHA class was the strongest independent predictor of ADT. In conclusion, primary prevention NYHA-I ICD patients showed a higher incidence of ADT compared with NYHA-II-III ICD patients. These results strongly suggest that primary prevention NYHA-I patients with a LVEF ≤35% are likely to benefit from ICD therapy and should not be excluded from a potentially life-saving therapy.
Subject(s)
Asymptomatic Diseases , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Electric Countershock/statistics & numerical data , Heart Failure/therapy , Stroke Volume , Aged , Cardiac Resynchronization Therapy Devices , Female , Heart Failure/physiopathology , Humans , Male , Middle Aged , Mortality , Primary Prevention , Proportional Hazards Models , Retrospective StudiesABSTRACT
Coronary venous stenosis is an uncommon finding in patients referred for cardiac resynchronization therapy device implantation. Nonetheless, it may result in suboptimal lead positioning for chronic left ventricular (LV) pacing. Coronary venous angioplasty is a technique that can be performed relatively easily and safely to enable LV lead passage beyond a stenosis.
ABSTRACT
Early identification and treatment of the vulnerable plaque, that is, a coronary artery lesion with a high likelihood of rupture leading to an acute coronary syndrome, have gained great interest in the cardiovascular research field. Postmortem studies have identified clear morphological characteristics associated with plaque rupture. Recent advances in invasive and noninvasive coronary imaging techniques have empowered the clinician to identify suspected vulnerable plaques in vivo and paved the way for the evaluation of therapeutic agents targeted at reducing plaque vulnerability. Local treatment of vulnerable plaques by percutaneous coronary intervention and systemic treatment with anti-inflammatory and low-density lipoprotein-lowering drugs are currently being investigated in large randomized clinical trials to assess their therapeutic potential for reducing adverse coronary events. Results from these studies may enable a more patient-tailored strategy for the treatment of coronary artery disease.
Subject(s)
Acute Coronary Syndrome/prevention & control , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Early Diagnosis , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/therapy , Acute Coronary Syndrome/complications , Coronary Artery Disease/complications , Coronary Vessels/diagnostic imaging , Humans , Plaque, Atherosclerotic/complicationsABSTRACT
OBJECTIVE: In patients with acute myocardial infarction (AMI), coronary vasomotor function is impaired in the myocardial territory supplied by the culprit artery and in remote myocardium supplied by angiographically normal vessels. The aim was to investigate the temporal evolution of coronary vasodilatory reserve in patients with AMI by use of [(15)O]H2O positron emission tomography, after successful percutaneous coronary intervention. METHODS: 44 patients with AMI and successful revascularisation by percutaneous coronary intervention were included. Subjects were examined 1â week and 3â months after AMI with [(15)O]H2O positron emission tomography to assess the coronary flow reserve (CFR). CFR was defined as the ratio of myocardial blood flow (MBF) during hyperaemia and rest. Additionally, 45 age-matched and sex-matched subjects underwent similar scanning procedures and served as controls. RESULTS: At baseline, CFR averaged 1.81±0.66 in infarcted myocardium versus 2.51±0.81 in remote myocardium (p<0.01). In comparison, CFR in the control group averaged 4.16±1.45 (p=0.001 vs both). During follow-up, the CFR increased to 2.74±0.85 in infarcted myocardium (p<0.01), and to 2.85±0.70 in remote myocardium (p<0.01). This was predominantly due to an increase in hyperaemic MBF, from 1.62±0.54 mL/min/g to 2.19±0.68â mL/min/g in infarcted myocardium (p<0.001), and 2.17±0.54 mL/min/g to 2.60±0.65â mL/min/g in remote myocardium (p<0.001). CONCLUSIONS: CFR in infarcted and remote myocardium is impaired 1â week after AMI. After 3â months vasomotor function partially recovers. However, as compared with control patients, MBF remains impaired in culprit and reference territories in patients with AMI. CLINICAL TRIAL REGISTRATION: NTR3164.
Subject(s)
Coronary Vessels/innervation , Fractional Flow Reserve, Myocardial , Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Vasodilation , Vasomotor System/physiopathology , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/physiopathology , Myocardial Perfusion Imaging/methods , Oxygen Radioisotopes , Positron-Emission Tomography , Predictive Value of Tests , Radiopharmaceuticals , Recovery of Function , Time Factors , Treatment Outcome , Vascular ResistanceABSTRACT
Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death in adolescence, and may lead to heart failure at any age. However, significant heterogeneity in the clinical course and phenotypic expression exists. Next to left ventricular hypertrophy, an impaired myocardial blood flow (MBF) during stress and inefficient cardiac metabolism are other characteristics of HCM. Studies using positron emission tomography (PET) have led to an enhanced understanding of the role that myocardial ischaemia and impaired energetics play in the clinical course of HCM. The blunted vasodilator reserve in the absence of an epicardial coronary stenosis is the result of microvascular dysfunction. Microvascular dysfunction, in turn, represents a predisposing factor for myocardial ischaemia, which may lead to cardiac dysfunction and fibrosis. Correspondingly, the severity of microvascular dysfunction has been shown to serve as a major predictor of mortality. Myocardial energetics in HCM has been studied with similar interest as mounting evidence suggests that mechano-energetic uncoupling may play a central role in its pathogenesis. Although prognostic data related to an impaired energetic state in HCM are lacking, it may hold prognostic relevance. Consequently, enhancing perfusion and restoring energetics have gained considerable attention as potential strategies to alter the natural course of HCM. In this regard, myocardial perfusion and metabolic imaging serves as a valuable tool to monitor the effects of therapeutic interventions on the pathophysiology of HCM.
Subject(s)
Cardiomyopathy, Hypertrophic/diagnostic imaging , Coronary Circulation/physiology , Myocardial Ischemia/diagnostic imaging , Oxygen Consumption/physiology , Physical Endurance , Cardiomyopathy, Hypertrophic/physiopathology , Cardiomyopathy, Hypertrophic/therapy , Energy Metabolism/physiology , Female , Heart Function Tests , Humans , Male , Myocardial Contraction/physiology , Myocardial Ischemia/physiopathology , Myocardial Ischemia/therapy , Positron-Emission Tomography/methods , Sensitivity and Specificity , Severity of Illness Index , Tomography, Emission-Computed, Single-Photon/methodsABSTRACT
BACKGROUND: Myocardial washout kinetics of carbon-11 labelled acetate ([11C]acetate) by positron emission tomography (PET) closely correlate with myocardial oxygen consumption (MVO2). Analysis of the tissue time activity curve by conventional monoexponential curve fitting, however, does not account for spillover effects and recirculating 11C activity. In theory, a compartment model considering variations of the arterial input function and metabolic 11C contamination, could improve consistency of MVO2 estimations. The objective of the study was to investigate this hypothesis. METHODS: Nineteen healthy volunteers were studied under resting conditions with [11C]acetate PET. Time activity curves were analysed by automated monoexponential curve fitting and a single-tissue compartment model to obtain Kmono and k2, as noninvasive indices of MVO2. Subsequently, Kmono and k2 were related to the rate-pressure product, as an indirect marker of MVO2. RESULTS: The rate-pressure product was significantly correlated to Kmono (r=0.46, P=0.047) and k2 (r=0.75, P<0.001). CONCLUSION: The results of this study suggest that a single-tissue compartment model yields more accurate noninvasive estimates of MVO2 by the use of [11C]acetate PET in humans, in comparison with monoexponential curve fitting.
Subject(s)
Acetates , Carbon , Models, Biological , Myocardium/metabolism , Oxygen/metabolism , Positron-Emission Tomography , Acetates/metabolism , Carbon/metabolism , Female , Heart/physiology , Hemodynamics , Humans , Male , Middle AgedABSTRACT
AIMS: Next to left ventricular (LV) hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by microvascular dysfunction and reduced myocardial external efficiency (MEE). Insights into the presence of these abnormalities as early markers of disease are of clinical importance in risk stratification, and development of therapeutic approaches. Therefore, the aim was to investigate myocardial perfusion and energetics in genotype-positive, phenotype-negative HCM subjects (carriers). METHODS AND RESULTS: Fifteen carriers of an MYBPC3 mutation underwent [(15)O]water positron emission tomography (PET) to assess myocardial blood flow (MBF). [(11)C]acetate PET was performed to obtain myocardial oxygen consumption (MVO(2)). By use of cardiovascular magnetic resonance imaging, LV volumes and mass were defined to calculate MEE, i.e. the ratio between external work and MVO(2). Eleven healthy, genotype-negative, family relatives underwent similar scanning protocols to serve as a control group. Left ventricular mass was comparable between carriers and controls (93 ± 25 vs. 99 ± 21 g, P= 0.85), as was MBF at rest (1.19 ± 0.34 vs. 1.18 ± 0.32 mL min(-1) g(-1), P= 0.92), and during hyperaemia (3.87 ± 0.75 vs. 3.96 ± 0.86 mL min(-1) g(-1), P= 0.77). Myocardial oxygen consumption averaged 0.137 ± 0.057 mL min(-1) g(-1) in carriers and was not significantly different from controls (0.125 ± 0.043 mL min(-1) g(-1), P= 0.29). Cardiac work, however, was slightly reduced in carriers (7398 ± 1384 vs. 9139 ± 2484 mmHg mL in controls, P= 0.08). As a consequence, MEE was significantly decreased in carriers (27 ± 10 vs. 36 ± 8% in controls, P= 0.02). CONCLUSION: Carriers display reduced myocardial work generation in relation to oxygen consumption, in the absence of hypertrophy and flow abnormalities. Hence, impaired myocardial energetics may constitute a primary component of HCM pathogenesis.
Subject(s)
Cardiomyopathy, Hypertrophic/genetics , Carrier Proteins/genetics , Coronary Vessels/physiopathology , DNA/genetics , Microvessels/physiopathology , Mutation , Ventricular Function, Left/physiology , Adult , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/physiopathology , Carrier Proteins/metabolism , Coronary Circulation , Female , Genetic Predisposition to Disease , Heterozygote , Humans , Magnetic Resonance Imaging, Cine , Male , Middle Aged , Myocardium/metabolism , Myosins , Oxygen Consumption , Positron-Emission Tomography , Prognosis , Regional Blood FlowABSTRACT
We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (E(cc)) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean E(cc) was -14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and -17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, E(cc) and DCE in the septum (-13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (-16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and E(cc) were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to E(cc) (r = -0.45, p <0.001) and DCE (r = -0.31, p <0.001). Multivariate analysis revealed that E(cc) was independently related to hMBF (beta -0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction.