Martin Penicka

Improvement of Left Ventricular Function After Cardiac Resynchronization Therapy Is Predicted by Tissue Doppler Imaging Echocardiography

Background—Cardiac resynchronization therapy was shown to reverse left ventricular (LV) remodeling in patients with congestive heart failure (CHF). However, the prediction of benefit is controversial. We aimed to investigate predictive factors of LV functional recovery and reversed remodeling after biventricular pacing. Methods and Results—Forty-nine consecutive patients with CHF and a wide QRS complex (182±32 ms) were studied by echocardiography before resynchronization. Intraventricular and interventricular asynchrony and their combination were assessed by pulsed-wave tissue Doppler imaging from measurements of regional electromechanical coupling times in basal segments of the right and left ventricle. At 6-month follow-up, responders were defined by a relative increase in LV ejection fraction ≥25% compared with baseline (n=27). Receiver operating curve analysis revealed the degree of intraventricular asynchrony (area under the curve=0.77), interventricular asynchrony (area under the curve=0.69), and their combination (area under the curve=0.84) as the best predictors of functional recovery after resynchronization. In addition, the degree of intraventricular and interventricular asynchrony correlated significantly with the improvement of LV ejection fraction (r =0.73, P <0.0001), end-diastolic diameter (r =−0.59, P <0.0001), and end-systolic diameter (r =−0.48, P <0.001) at follow-up. QRS duration and conventional echo-Doppler indices were not predictive of reversed LV remodeling. Conclusions—In patients with CHF, the degree of intraventricular and interventricular asynchrony and their combination are the best predictive factors of LV functional recovery and reversed remodeling after cardiac resynchronization therapy.

Heart Failure With Preserved Ejection Fraction in Outpatients With Unexplained Dyspnea : A Pressure-Volume Loop Analysis

OBJECTIVES The aim of the present study was to diagnose heart failure with preserved ejection fraction (HFPEF) in outpatients with unexplained chronic dyspnea and to elucidate its underlying mechanisms in this population using invasive pressure-volume loop analysis. BACKGROUND The diagnosis of HFPEF in stable outpatients with unexplained dyspnea is difficult. METHODS Thirty patients (age 67 +/- 8.6 years, 27% males) with preserved left ventricular (LV) ejection fraction (>50%) and unexplained chronic New York Heart Association functional class II to III dyspnea underwent heart catheterization. Patients with significant coronary artery stenosis (>50%) were excluded. Pressure-volume loops were assessed using a conductance catheter at rest, hand-grip exercise, leg lifting, and nitroprusside and dobutamine infusion. RESULTS Twenty (66%) patients showed LV end-diastolic pressure >16 mm Hg (HFPEF), whereas the remaining 10 patients served as controls. Patients with HFPEF had significantly higher end-diastolic stiffness (0.205 +/- 0.074 vs. 0.102 +/- 0.017, p < 0.001) at rest, and their end-diastolic pressure-volume relationship showed a consistent upward and leftward shift during all hemodynamic interventions compared with controls. Regarding the underlying mechanism of HFPEF, 14 (70%) patients had markedly increased end-diastolic stiffness, which was considered a sufficient single pathology to induce increased LV end-diastolic pressure. Four (20%) patients showed a concomitant presence of moderately increased stiffness and severe LV dyssynchrony, and the remaining 2 (10%) patients, with normal stiffness, showed significant exercise-induced mitral regurgitation at hand-grip exercise. If the invasive pressure measurements were absent, only 5 (25%) of the outpatients with HFPEF fulfilled the European Society of Cardiology definition of HFPEF. CONCLUSIONS A significant proportion of stable outpatients with unexplained chronic dyspnea may have HFPEF. In the patients whom we studied, increased LV stiffness, dyssynchrony, and dynamic mitral regurgitation were the major mechanisms underlying development of HFPEF.

Echocardiographic reference ranges for normal cardiac chamber size: results from the NORRE study.

AIMS Availability of normative reference values for cardiac chamber quantitation is a prerequisite for accurate clinical application of echocardiography. In this study, we report normal reference ranges for cardiac chambers size obtained in a large group of healthy volunteers accounting for gender and age. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following chamber quantitation protocols approved by the European Association of Cardiovascular Imaging. METHODS A total of 734 (mean age: 45.8 ± 13.3 years) healthy volunteers (320 men and 414 women) were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was performed on all subjects following pre-defined protocols. There were no gender differences in age or cholesterol levels. Compared with men, women had significantly smaller body surface areas, and lower blood pressure. Quality of echocardiographic data sets was good to excellent in the majority of patients. Upper and lower reference limits were higher in men than in women. The reference values varied with age. These age-related changes persisted for most parameters after normalization for the body surface area. CONCLUSION The NORRE study provides useful two-dimensional echocardiographic reference ranges for cardiac chamber quantification. These data highlight the need for body size normalization that should be performed together with age-and gender-specific assessment for the most echocardiographic parameters.

Predictors of Improvement of Unrepaired Moderate Ischemic Mitral Regurgitation in Patients Undergoing Elective Isolated Coronary Artery Bypass Graft Surgery

Background— The persistence of moderate ischemic mitral regurgitation (IMR) after isolated coronary artery bypass graft surgery is an important independent predictor of long-term mortality. The aim of the present study was to identify predictors of postoperative improvement in moderate IMR in patients with ischemic heart disease undergoing elective isolated coronary artery bypass graft surgery. Methods and Results— The study population consisted of 135 patients with ischemic heart disease (age, 65±9 years; 81% male) and moderate IMR undergoing isolated coronary artery bypass graft surgery. Fourteen patients died before the 12-month follow-up echocardiography and were excluded. At the 12-month follow-up, 57 patients showed no or mild IMR (improvement group), whereas 64 patients failed to improve (failure group). Before coronary artery bypass graft surgery, the improvement group had significantly more viable myocardium and less dyssynchrony between papillary muscles than the failure group (P<0.001). All other preoperative parameters were similar in both groups. Large extent (≥5 segments) of viable myocardium (odds ratio, 1.45; 95% confidence interval, 1.22 to 1.89; P<0.001) and absence (<60 ms) of dyssynchrony (odds ratio, 1.49; 95% confidence interval, 1.29 to 1.72; P<0.001) were independently associated with improvement in IMR. The majority (93%) of patients with viable myocardium and an absence of dyssynchrony showed an improvement in IMR. In contrast, only 34% and 18% of patients with dyssynchrony and nonviable myocardium, respectively, showed an improvement in IMR, whereas 32% and 49%, respectively, of these patients showed worsening of IMR (P<0.001). Conclusion— Reliable improvement in moderate IMR by isolated coronary artery bypass graft surgery was observed only in patients with concomitant presence of viable myocardium and absence of dyssynchrony between papillary muscles.

Early Tissue Distribution of Bone Marrow Mononuclear Cells After Transcoronary Transplantation in a Patient With Acute Myocardial Infarction

A 57-year-old man with no history of coronary artery disease was admitted for acute anterior ST-segment–elevation myocardial infarction caused by an occlusion of the proximal left anterior descending (LAD) coronary artery. The culprit artery was recanalized with direct stenting with an optimal result. Left ventricular ejection fraction was 40% with anteroapicoseptal akinesia. A positron-emission tomography study demonstrated reduced perfusion and borderline fluorine-18-fluorodeoxyglucose uptake in apical segments and adjacent anterior and septal wall, suggesting reduced viability in the distal LAD territory. Nine days after infarction, the patient underwent autologous bone marrow stem cell transplantation as a part of a research protocol. Bone marrow blood was aspirated under local anesthesia from both iliac crests. A total of 27.4×108 of …

One Day Kinetics of Myocardial Engraftment After Intracoronary Injection of Bone Marrow Mononuclear Cells in Patients with Acute and Chronic Myocardial Infarction.

Objective: To investigate the kinetics of myocardial engraftment of bone marrow-derived mononuclear cells (BMNCs) after intracoronary injection using 99mTc-d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) nuclear imaging in patients with acute and chronic anterior myocardial infarction. Design: Nuclear imaging-derived tracking of BMNCs at 2 and 20 h after injection in the left anterior descending (LAD) coronary artery. Setting: Academical cardiocentre. Patients: Five patients with acute (mean (SD) age 58 (11) years; ejection fraction range 33–45%) and five patients with chronic (mean (SD) age 50 (6) years; ejection fraction range 28–34%) anterior myocardial infarction. Interventions: A total of 24.2×108–57.0×108 BMNCs (20% labelled with 700–1000 MBq 99mTc-HMPAO) were injected in the LAD coronary artery. Results: At 2 h after BMNC injection, myocardial activity was observed in all patients with acute (range 1.31–5.10%) and in all but one patient with chronic infarction (range 1.10–3.0%). At 20 h, myocardial engraftment was noted only in three patients with acute myocardial infarction, whereas no myocardial activity was noted in any patient with chronic infarction. Conclusions: Engraftment of BMNCs shows dynamic changes within the first 20 h after intracoronary injection. Persistent myocardial engraftment was noted only in a subset of patients with acute myocardial infarction.

Relationship of visually assessed apical rocking and septal flash to response and long-term survival following cardiac resynchronization therapy (PREDICT-CRT)

AIMS Apical rocking (ApRock) and septal flash (SF) are often observed phenomena in asynchronously contracting ventricles. We investigated the relationship of visually assessed ApRock and SF, reverse remodelling, and long-term survival in cardiac resynchronization therapy (CRT) candidates. METHODS AND RESULTS A total of 1060 patients eligible for CRT underwent echocardiographic examinations before and 12 ± 6 months after device implantation. Three blinded physicians were asked to visually assess the presence of ApRock and SF before device implantation and also their correction by CRT 12 ± 6 months post-implantation. Patients with a left ventricular (LV) end-systolic volume decrease of ≥15% during the first year of follow-up were regarded as responders. Patients were followed for a median period of 46 months (interquartile range: 27-65 months) for the occurrence of death of any cause. If corrected by CRT, visually assessed ApRock and SF were associated with reverse remodelling with a sensitivity of 84 and 79%, specificity of 79 and 74%, and accuracy of 82 and 77%, respectively. ApRock (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.30-0.53, P < 0.0001) and SF (HR 0.45 [CI 0.34-0.61], P < 0.001) were independently associated with lower all-cause mortality after CRT and had an incremental value over clinical variables and QRS width for identifying CRT responders. Both the absence of ApRock/SF and unsuccessful correction of ApRock/SF despite CRT were associated with a high risk for non-response and an unfavourable long-term survival. CONCLUSION A specific LV mechanical dyssynchrony pattern, characterized by ApRock and SF, is associated with a more favourable long-term survival after CRT. Both parameters are also indicators of an effective therapy.

The Effects of Candesartan on Left Ventricular Hypertrophy and Function in Nonobstructive Hypertrophic Cardiomyopathy: A Pilot, Randomized Study

Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ss-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy.

One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations. Clinical Trial Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913613.

Thr164Ile polymorphism of β2-adrenergic receptor negatively modulates cardiac contractility: implications for prognosis in patients with idiopathic dilated cardiomyopathy

Background: β2-adrenergic receptor Thr164Ile (threonine (Thr) is replaced by an isoleucine (Ile) at codon 164) polymorphism was postulated to contribute to lower exercise tolerance and poor prognosis in patients with congestive heart failure. However, heart failure is associated with several abnormalities of β receptor signalling, and underlying mechanisms are not clear. Objectives: To investigate whether Thr164Ile polymorphism negatively modulates myocardial contractile performance and is associated with adverse long-term prognosis of patients with congestive heart failure. Methods: Among 55 subjects, cardiac contractile response to the β2-adrenergic receptor agonist terbutaline was assessed from the peak myocardial velocity of systolic shortening (Sm) in 18 subjects with the Ile-164 variant and 37 matched controls. In total, 24 subjects had normal left ventricular (LV) function and 31 presented with congestive heart failure due to idiopathic dilated cardiomyopathy. Results: In patients with normal LV function, peak terbutaline-induced increase (Δ) in Sm was lower in subjects with the Ile-164 variant than in controls (Δ33% (4%) vs Δ56% (4%), p<0.01). In patients with heart failure, subjects with Ile-164 showed further severe reduction of β2-adrenergic-mediated increase in Sm as compared with controls with heart failure (Δ20% (5%) vs Δ39% (4%), p<0.05). Patients with heart failure with Ile-164 showed a severely blunted force–frequency relationship in response to agonist stimulation. At 2-years of follow-up, patients with heart failure with the Ile-164 variant showed higher incidence of adverse events than controls with heart failure (75% (6/8)] vs 30% (7/23), p<0.05). Conclusions: The β2-adrenergic Thr164Ile polymorphism directly modulates adrenergic-mediated cardiac responses in patients with normal and failing myocardium. Furthermore, blunted β2 adrenergic-mediated myocardial contractile response in patients with Ile-164 variant seems to adversely modulate the course of congestive heart failure.