Magdalena Kostkiewicz

Left ventricular geometry and function in patients with aortic stenosis: gender differences

BACKGROUND Gender differences in cardiac size have been described in normal and pathological conditions in human and animals. Sex determination of a pattern of hypertrophy as a response to pressure overload has not been extensively evaluated and is still poorly understood in humans. METHODS AND RESULTS To investigate the influence of gender in the left ventricle remodelling and preservation of the left ventricle function 195 adults (140 men and 55 women) with isolated aortic stenosis were evaluated. The mean age was 52 +/- 11 years for men and 53 +/- 13 years for women. All the patients had similar degree of aortic stenosis finally treated with valve replacement, similar clinical status and no signs of coronary artery disease in coronary angiograms. On echocardiography the left ventricle of women had a smaller the end systolic (30.5 +/- 7.8 vs. 39.4 +/- 11.2, P<0.001) and the end diastolic (49.4 +/- 9 vs. 57.3 +/- 11, P<0.001) chamber size. The female left ventricle generated a higher relative wall thickness (0.65 +/- 0.21 vs. 0.52 +/- 0.12, P<0.01), a greater fractional shortening (35.3 +/- 8.5 vs. 32.0 +/- 9.0, P<0.01) and a higher ejection fraction (64.4 +/- 12.7 vs. 57.5 +/- 14.6, P<0.001). The left ventricle posterior wall thickness and the septal thickness indexes were similar in both groups. There were also significant differences between the two groups in the left ventricle mass index. CONCLUSIONS Gender has an important influence on the left ventricle adaptation pattern to pressure overload due to aortic stenosis. Women developed a greater degree of left ventricle hypertrophy documented as changes in left ventricle geometry (increased relative wall thickness, left ventricular mass) and left ventricle function (fractional shortening and ejection fraction).

Assessment of myocardial perfusion in patients with coronary artery disease. Comparison of myocardial contrast echocardiography and 99mTc MIBI single photon emission computed tomography.

BACKGROUND Myocardial perfusion (MP) can be assessed in real time when using a low mechanical index (MI) and harmonic imaging following an intravenous injection of contrast agent. The aim of the study was to determine the feasibility and accuracy of the real-time imaging of contrast echocardiography (MCE) for detecting myocardial perfusion defects at rest and during dobutamine stress echocardiography (DE) compared with 99m Tc MIBI SPECT. The study group consisted of 44 patients (24 men, 20 women, mean age 58.9+/-7.8) with suspected coronary artery disease (CAD). All patients underwent DE. Wall motion (WM) and segmental perfusion were estimated in real time before and at peak stress using a low MI (0.4) after 0.3 ml bolus injections of intravenous Optison. All patients underwent a rest and exercise 99mTc MIBI SPECT study (SPECT). A 16-segment model of the left ventricle was used for the analysis of MP, WM and SPECT by a blinded reviewer. All patients underwent coronary angiography. Significant coronary artery disease was defined as >60% luminal diameter stenosis. RESULTS All patients had significant CAD. Twenty-nine patients had single-vessel and 15 patients had double-vessel disease. For all patients, agreement between MCE and SPECT was 89%, between MCE and WM -86%, and between SPECT and WM -82%. The agreement between MCE and SPECT for LAD, RCA and Cx territories was 81, 91 and 73%, respectively. The sensitivity of MCE and SPECT for detecting perfusion defects due to significant CAD (confirmed angiographically) was 97% and 93%, respectively, and the specificity was 93 and 84%, respectively. CONCLUSION MCE in real-time imaging with Optison has significant potential for the identification of MP abnormalities. MCE correlates very well with SPECT images.

Infarct size determines myocardial uptake of CD34+ cells in the peri-infarct zone: results from a study of (99m)Tc-extametazime-labeled cell visualization integrated with cardiac magnetic resonance infarct imaging.

Background— Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34+ cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size. Methods and Results— Thirty-one subjects (age, 36–69 years; 28 men) with primary percutaneous coronary intervention–treated anterior ST-segment–elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/mL [limits, 58–356 ng/mL]) and sustained LVEF depression at ⩽45% were recruited. On day 10 (days 7–12), 4.3×106 (0.7–9.9×106) 99mTc-extametazime–labeled autologous bone marrow CD34+ cells (activity, 77 MBq [45.9–86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). 99mTc-methoxyisobutyl isonitrile (99mTc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2–11) (of 17) segments with definitely abnormal/absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4–45.9 g), and infarct border zone mass was 29.8 g (3.9–60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%–9.9%) of labeled cell activity localized in the myocardium (whole-body planar &ggr; scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass (r=0.84, P<0.0001); it also correlated with peak TnI (r=0.76, P<0.001), severely-abnormal/absent perfusion segment number (r=0.45, P=0.008), and late gadolinium-enhanced infarct core (r=0.58, P=0.0003) but not with echocardiography LVEF (r=−0.07, P=0.68) or gated single-photon emission computed tomography LVEF (r=−0.28, P=0.16. The correlation with cardiac magnetic resonance imaging-LVEF was weak (r=−0.38; P=0.04). Conclusions— This largest human study with labeled bone marrow CD34+ cell transcoronary transplantation after recent ST-segment–elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.

Heart structure and function in patients with generalized autoimmune diseases: echocardiography with tissue Doppler study.

Objective Heart pathology strongly infl uences the course and prognosis of patients with generalized autoimmune diseases. In spite of autoimmunity being a common denominator of these diseases, systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and dermato/polymyositis (DPM) diff er signifi cantly in the pathogenesis of organ damage. The aim of the study was to compare pathologic changes in heart structure and function in these diseases by means of standard echocardiography and tissue Doppler (TDE). Material and methods Four groups were examined: 60 SSc, 60 SLE and 15 DPM patients in stable clinical conditions and 30 healthy control subjects. Echocardiography with TDE was performed with the assessment of systolic (S) and diastolic (E) velocities of mitral and tricuspid annuli. Results Heart in SSc was characterized by signifi cant diastolic left ventricular dysfunction (mitral E 8.61 ± 2.3 cm/s vs. 12.4 ± 3.5 cm/s in the control group; P < 0.01) with preserved systolic function (mitral S 7.85 ± 1.5 cm/s vs. 7.95 ± 0.9 cm/s in control group; ns). SLE and DPM resulted mainly in pathologic thickening of valvular leafl ets and/or pericardium [mitral or aortic leafl ets thickened in 38 (63.3%) of SLE patients, 7 (46.7%) of DPM patients; pericardium thickened in 36 (60%) of SLE patients]. Pulmonary capillary wedge pressure was elevated in SSc (13.8 ± 3.5 mmHg) and DPM (13.2 ± 2.5 mmHg) patients, as compared to the control group (9.2 ± 3.7 mmHg, P < 0.01). Right ventricular systolic and diastolic dysfunction was frequent irrespective of the presence or absence of pulmonary hypertension. Conclusions Echocardiography with TDE reveals characteristic pathology in diff erent forms of generalized autoimmune diseases refl ecting their diff erent pathogenetic mechanisms. Overproduction of collagen in SSc results in diastolic left ventricular dysfunction, while generalized infl ammation in SLE and DPM leads mainly to pathologic changes on valvular leafl ets and/or pericardium. Interestingly, right ventricular dysfunction is common in all diseases analyzed, regardless of the presence of pulmonary hypertension. Echocardiography, preferably with TDE, could add valuable information about usually asymptomatic heart pathology in an individual patient with generalized autoimmune disease.

Long-term outcome of coronary balloon angioplasty in diabetic patients

Diabetes is recognised to increase morbidity and mortality after coronary revascularization. We compared clinical outcomes in mean 5-year-long follow-up of coronary balloon angioplasty in diabetic and non-diabetic patients. We studied 621 patients undergoing elective angioplasty from 1987 to 1996. There were 60 (9.7%) patients with diabetes who were compared with 561 non-diabetic patients. Diabetics were older, more often obese, less frequently were current smokers, and less frequently had hypercholesterolaemia. Diabetic patients in comparison with non-diabetics had lower ejection fraction and more frequently had angioplasty of complex (B2 or C) lesions, but there were no differences between both groups in the other clinical and angiographic risk factors. Clinical success of angioplasty, as well as complications rate were similar in both groups. In follow-up restenosis occurred more frequently in diabetics (46.3 vs. 32.2%, P=0.03), resulting in significantly higher re-intervention rate (50.0 vs. 35.4%, P=0.03). Especially diabetic patients were more frequently referred to CABG (20.4 vs. 9. 9%, P=0.02). There were no significant differences in deaths (1.9 vs. 2.8%) and myocardial infarction (3.7 vs. 4.4%). Diabetics presented worse CCS status at the end of observation (Class 0 and I - 61.1 vs. 74.4%, P=0.037). Angioplasty proved to be a safe procedure in diabetic patients. Despite higher restenosis and re-intervention rate in diabetics, mortality as well as myocardial infarction rate was the same in both groups during mean 5-year follow-up.

Myocardial regeneration strategy using Wharton's jelly mesenchymal stem cells as an off-the-shelf 'unlimited' therapeutic agent: results from the Acute Myocardial Infarction First-in-Man Study.

Introduction In large-animal acute myocardial infarction (AMI) models, Whartons jelly (umbilical cord matrix) mesenchymal stem cells (WJMSCs) effectively promote angiogenesis and drive functional myocardial regeneration. Human data are lacking. Aim To evaluate the feasibility and safety of a novel myocardial regeneration strategy using human WJMSCs as a unique, allogenic but immuno-privileged, off-the-shelf cellular therapeutic agent. Material and methods The inclusion criterion was first, large (LVEF ≤ 45%, CK-MB > 100 U/l) AMI with successful infarct-related artery primary percutaneous coronary intervention reperfusion (TIMI ≥ 2). Ten consecutive patients (age 32–65 years, peak hs-troponin T 17.3 ±9.1 ng/ml and peak CK-MB 533 ±89 U/l, sustained echo LVEF reduction to 37.6 ±2.6%, cMRI LVEF 40.3 ±2.7% and infarct size 20.1 ±2.8%) were enrolled. Results 30 × 106 WJMSCs were administered (LAD/Cx/RCA in 6/3/1) per protocol at ≈ 5–7 days using a cell delivery-dedicated, coronary-non-occlusive method. No clinical symptoms or ECG signs of myocardial ischemia occurred. There was no epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45 ±8 vs. 44 ±9, p = 0.51), and no patient showed hs-troponin T elevation (0.92 ±0.29 ≤ 24 h before vs. 0.89 ±0.28 ≤ 24 h after; decrease, p = 0.04). One subject experienced, 2 days after cell transfer, a transient temperature rise (38.9°C); this was reactive to paracetamol with no sequel. No other adverse events and no significant arrhythmias (ECG Holter) occurred. Up to 12 months there was one new, non-index territory lethal AMI but no adverse events that might be attributable to WJMSC treatment. Conclusions This study demonstrated the feasibility and procedural safety of WJMSC use as off-the-shelf cellular therapy in human AMI and suggested further clinical safety of WJMSC cardiac transfer, providing a basis for randomized placebo-controlled endpoint-powered evaluation.

Prognostic value of carotid intima-media thickness in detection of coronary atherosclerosis in patients with calcified aortic valve stenosis.

Aortic stenosis (AS) coexists with coronary artery disease (CAD) in at least 30% of patients. Patients with concomitant CAD may benefit from simultaneous coronary bypass grafting. This study aimed to evaluate the prognostic value of carotid intima‐media thickness (IMT) in patients with AS in assessing concomitant CAD.

Prognostic value of nitrate enhanced Tc99m MIBI SPECT study in detecting viable myocardium in patients with coronary artery disease.

Background: Assessing the viability in akinetic myocardium is vital for predicting functional recovery after therapeutic management in patients with chronic coronary artery disease (CAD) and depressed left ventricular (LV) function. The present study aimed to evaluate the efficacy of Tc99m MIBI SPECT enhanced with nitroglycerine infusion in detecting myocardial viability, as well as to asses the relationship between the myocardial viability and the subsequent treatment and outcome of patients. Methods and results: Sixty-seven consecutive patients with CAD and LV dysfunction (LV ejection fraction 36.6 ± 8.4%) underwent Tc99m MIBI imaging – at rest and during intravenous nitroglycerine infusion – for viability assessment. Fourteen patients were treated pharmacologically (Group I), and fifty-three (Group II) were submitted to coronary revascularization (PTCR or CABG). Fifteen major cardiac events were observed during 25 months of the follow-up. A significantly worse event-free survival was registered in the subjects of Group I than in Group II subjects. The prognostic predictors of cardiac events were: (1) the number of viable, non-revascularized segments in perfusion imaging (p < 0.001), (2) the severity of the disease assessed by coronary angiography (p < 0.05). Conclusions: Viability detection in nitroglycerine infusion enhanced Tc99m MIBI imaging offers significant prognostic value in patients with CAD after myocardial infarction. Patients with preserved viability showed better prognosis after revascularization than those treated pharmacologically.

Myocardial ischemia assessed by Tc99m MIBI SPECT and left ventricle regional systolic and diastolic function evaluated by tissue Doppler echocardiography

Background: Tc99m MIBI single-photon emission computed tomography (SPECT) study facilitates the evaluation of the regional myocardial perfusion and tissue Doppler echocardiography imaging facilitates the quantitative assessment of the regional systolic and diastolic function of the myocardium. The aim of the study was an assessment of the correlation between regional rest myocardial perfusion defects and regional rest systolic and diastolic myocardial velocities in patients with ischemic heart disease (IHD). Material and methods: In 40 IHD patients (33 men, 7 women) aged 43–74 years (mean 56 years) rest SPECT imaging with Tc99m MIBI and rest tissue Doppler examinations were performed. The control group consisted of 35 healthy sex and age matched pesons. The left ventricle was divided into 13 segments. The number of non-perfused segments in three myocardial perfusion regions (left anterior descending artery, circumflex artery, right coronary artery) was assessed in IHD patients. During tissue Doppler examination the maximal systolic and maximal early diastolic velocity of the myocardium in each segment were established in both examined groups. Results: The systolic and diastolic myocardial velocities were significantly lower in IHD group as compared to control group. In the IHD group statistically significant decrease of systolic and diastolic velocities in relation to the number of non-perfused segments was found. In comparing the linear regression slopes for systolic and for diastolic myocardial velocities in terms of intensification of perfusion defects, a more pronounced decrease in diastolic velocity was encountered. Conclusions: Both systolic and diastolic myocardial velocities are decreased in the myocardial regions with perfusion defects, but the reduction of the diastolic velocity is higher than the reduction of the systolic velocities. Thus our results indicate a good correlation between the intensity of perfusion abnormalities and myocardial velocities. The levels of diastolic dysfunction is more pronounced than the level of systolic dysfunction in the ischemic myocardium.

Effects of Trans-Endocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

Rationale: New therapies for refractory angina are needed. Objective: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina. Methods and Results: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P=0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months. Conclusion: Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.