Correction to: Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy.

The following information is missing from the Funding footnote on the first page of the published article: "This study was partly funded by NIH RO1 HL092985." The last/corresponding author is incorrectly listed on the first page of the published article: The correct name is Abraham MR.

Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy.

BACKGORUND: Quantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy. AIM: We compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm. METHODS: 13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares. RESULTS: All HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). CONCLUSIONS: Anatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.

Stress induced hypertensive response: should it be evaluated more carefully?

Various diagnostic methods have been used to evaluate hypertensive patients under physical and pharmacological stress. Several studies have shown that exercise hypertension has an independent, adverse impact on outcome; however, other prognostic studies have shown that exercise hypertension is a favorable prognostic indicator and associated with good outcome. Exercise hypertension may be encountered as a warning signal of hypertension at rest and future hypertensive left ventricular hypertrophy. The results of diagnostic stress tests support that hypertensive response to exercise is frequently associated with high rate-pressure product in hypertensives. In addition to the observations on high rate-pressure product and enhanced ventricular contractility in patients with hypertension, evaluation of myocardial contractility by Doppler tissue imaging has shown hyperdynamic myocardial function under pharmacological stress. These recent quantitative data in hypertensives suggest that hyperdynamic myocardial function and high rate-pressure product response to stress may be related to exaggerated hypertension, which may have more importance than that it has been already given in clinical practice.

Basal Septal Hypertrophy as the Early Imaging Biomarker for Adaptive Phase of Remodeling Prior to Heart Failure.

Hypertension plays a dominant role in the development of left ventricular (LV) remodeling and heart failure, in addition to being the main risk factor for coronary artery disease. In this review, we focus on the focal geometric and functional tissue aspects of the LV septal base, since basal septal hypertrophy (BSH), as the early imaging biomarker of LV remodeling due to hypertensive heart disease, is detected in cross-sectional clinic studies. In addition, the validation of BSH by animal studies using third generation microimaging and relevant clinical observations are also discussed in the report. Finally, an evaluation of both human and animal quantitative imaging studies and the importance of combined cardiac imaging methods and stress-induction in the separation of adaptive and maladaptive phases of the LV remodeling are pointed out. As a result, BSH, as the early imaging biomarker and quantitative follow-up of functional analysis in hypertension, could possibly contribute to early treatment in a timely fashion in the prevention of hypertensive disease progression to heart failure. A variety of stress stimuli in etiopathogenesis and the difficulty of diagnosing pure hemodynamic overload mediated BSH lead to an absence of the certain prevalence of this particular finding in the population.

Evolution of ventricular hypertrophy and myocardial mechanics in physiological and pathological hypertrophy.

Left ventricular hypertrophy (LVH) is an adaptive response to physiological or pathological stimuli, and distinguishing between the two has obvious clinical implications. However, asymmetric septal hypertrophy and preserved cardiac function are noted in early stages in both cases. We characterized the early anatomic and functional changes in a mouse model of physiological and pathological stress using serial echocardiography-based morphometry and tissue velocity imaging. Weight-matched CF-1 male mice were separated into Controls ( n = 10), treadmill Exercise 1 h daily for 5 days/wk ( n = 7), and transverse aortic constriction (TAC, n = 7). Hypertrophy was noted first in the left ventricle basal septum compared with other segments in Exercise (0.84 ± 0.02 vs. 0.79 ± 0.03 mm, P = 0.03) and TAC (0.86 ± 0.05 vs. 0.77 ± 0.04 mm, P = 0.02) at 4 and 3 wk, respectively. At 8 wk, eccentric LVH was noted in Exercise and concentric LVH in TAC. Septal E/E' ratio increased in TAC (32.6 ± 3.7 vs. 37 ± 6.2, P = 0.002) compared with the Controls and Exercise (32.3 ± 5.2 vs. 32.8 ± 3.8 and 31.2 ± 4.9 vs. 28.2 ± 5.0, respectively, nonsignificant for both). Septal s' decreased in TAC (21 ± 3.6 vs. 17 ± 4.2 mm/s, P = 0.04) but increased in Exercise (19.6 ± 4.1 vs. 29.2 ± 2.3 mm/s, P = 0.001) and was unchanged in Controls (20.1 ± 4.2 vs. 20.9 ± 5.1 mm/s, nonsignificant). With similar asymmetric septal hypertrophy and normal global function during the first 4-8 wk of pathological and physiological stress, there is an early marginal increase with subsequent decrease in systolic tissue velocity in pathological but early and progressive increase in physiological hypertrophy. Tissue velocities may help adjudicate between these two states when there are no overt anatomic or functional differences. NEW & NOTEWORTHY Pathological and physiological stress-induced ventricular hypertrophy have different clinical connotations but present with asymmetric septal hypertrophy and normal global function in their early stages. We observed a marginal but statistically significant decrease in systolic tissue velocity in pathological but progressive increase in velocity in physiological hypertrophy. Tissue velocity imaging could be an important tool in the management of asymmetric septal hypertrophy by adjudicating between these two etiologies when there are no overt anatomic or functional differences.

Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by 13N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy.

Vasodilator-induced transient left ventricular (LV) cavity dilation by positron emission tomography (PET) is common in patients with hypertrophic cardiomyopathy (HC). Because most patients with PET-LV cavity dilation lack obstructive epicardial coronary artery disease, we hypothesized that vasodilator-induced subendocardial hypoperfusion resulting from microvascular dysfunction underlies this result. To test this hypothesis, we quantified myocardial blood flow (MBF) (subepicardial, subendocardial, and global MBF) and left ventricular ejection fraction (LVEF) in 104 patients with HC without significant coronary artery disease, using 13NH3-PET. Patients with HC were divided into 2 groups, based on the presence/absence of LV cavity dilation (LVvolumestress/LVvolumerest >1.13). Transient PET-LV cavity dilation was evident in 52% of patients with HC. LV mass, stress left ventricular outflow tract gradient, mitral E/E', late gadolinium enhancement, and prevalence of ischemic ST-T changes after vasodilator were significantly higher in patients with HC with LV cavity dilation. Baseline LVEF was similar in the 2 groups, but LV cavity dilation+ patients had lower stress-LVEF (43 ± 11 vs 53 ± 10; p <0.001), lower stress-MBF in the subendocardial region (1.6 ± 0.7 vs 2.3 ± 1.0 ml/min/g; p <0.001), and greater regional perfusion abnormalities (summed difference score: 7.0 ± 6.1 vs 3.9 ± 4.3; p = 0.004). The transmural perfusion gradient, an indicator of subendocardial perfusion, was similar at rest in the 2 groups. Notably, LV cavity dilation+ patients had lower stress-transmural perfusion gradients (0.85 ± 0.22, LV cavity dilation+ vs 1.09 ± 0.39, LV cavity dilation-; p <0.001), indicating vasodilator-induced subendocardial hypoperfusion. The stress-transmural perfusion gradient, global myocardial flow reserve, and stress-LVEF were associated with LV cavity dilation. In conclusion, diffuse subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient LV cavity dilation in HC.

Could early septal involvement in the remodeling process be related to the advance hypertensive heart disease?

BACKGROUND: Quantitative imaging analyses showed an earlier septal wall involvement in hypertension. We planned to determine the effect of hypertension on regional myocardial performance index (MPI) in a hypertensive patient population. METHODS: We evaluated 119 hypertensive patients who were divided into gr. I: 57 patients without left ventricular hypertrophy (LVH), (53.1 ± 10 years), and gr. II: 62 patients with LVH (55.1 ± 9 years) using conventional and tissue doppler imaging. They were compared with gr. III, a sex-age-matched normal control group (37 subjects, 53.0 ± 10 years). RESULTS: We detected basal septal and basal lateral contraction time (CT), isovolumetric CT and relaxation time (IVRT) and MPI. EF was 68 ± 5 % in gr. I, 69 ± 5 % in gr. II, 69 ± 4 % in gr. III. LV mass index was 122 ± 11 g/m2 in gr. I, 148 ± 13 g/m2 in gr. II and 118 ± 13 g/m2 in gr. III. Concentric LVH was detected in gr. II (relative wall thickness = 0.49 ± 0.8). LV septal and lateral MPI were abnormal in both hypertensive groups (p < 0.0001). Septal MPI was correlated moderately with septal wall thickness (r = 0.447, p < 0.001). CONCLUSIONS: LV diastolic dysfunction becomes more severe in septal wall than lateral wall in hypertensive LVH. Septal myocardial performance is more dominantly affected by hypertension possibly due to earlier septal involvement in disease course. Septal MPI is correlated moderately with septal wall thickness.

Complete reverse remodeling in acute stress cardiomyopathy. Is preserved tissue contractility under stress related to reverse remodeling.

Acute stress cardiomyopathy is the unique disease which represents exaggerated and dysfunctional regions of the same cardiac tissue at the same episode. The impressive clinical course which involves the specific region is the stress-mediated exaggerated function of LV base under acutely developed stress induction. After abolishment of stress induction, dysfunctional part of LV which is the midapical myocardium undergoes a complete tissue functional recovery. The evolution of reverse remodeling in acute stress cardiomyopathy has been described using 2 and 3-dimensional echocardiography in the literature. This is the second report regarding reverse LV remodeling in acute stress cardiomyopathy in which we rather evaluate the underlying mechanisms leading complete reverse LV remodeling of dysfunctional myocardium. Therefore, we focus on the existence of preserved and exaggerated regional tissue under stress which possibly represents the predicted myocardial tissue recovery in this acute clinical entity. We also discuss the potential contribution of short-term disease course and lack of prior disease episodes to complete reverse remodeling differently from the heavy burden of chronic diseases leading to permanent tissue jeopardy.

Can quantitative regional myocardial dynamics contribute to the differential diagnosis of acute stress cardiomyopathy?

Acute stress-induced cardiomyopathy has excessive sympathetic stimulation, microvascular dysfunction similar to hypertension. Regional prominence of left ventricular (LV) septal base and stress-induced LV hypercontractility are the particular features of both acute and chronic stress-related conditions. Novel imaging methods have shown that stress-induced cavity dilation and myocardial wall abnormalities can be a reflection of underlying previous exaggerated hypertensive episodes due to sympathetic overdrive, which results in microvascular dysfunction. Hypertension-mediated chronic stress due to increased after load episodes is possibly the main reason for blunted LV myocardial wall motion capability in patients with stress-related exaggerated hypertension. In this short report, we discussed the interrelation of myocardial dynamics and stress-induced exaggerated hypertension episodes. In addition, quantitative echocardiographic methods which previously were used for description of particular features including LV regional dynamics in hypertensive heart disease can be an option in differential diagnosis of potential cases of acute stress-induced cardiomyopathy.

The effect of valsartan on left ventricular myocardial functions in hypertensive patients with left ventricular hypertrophy.

BACKGROUND: It has been shown by various diagnostic methodologies that angiotensin receptor blockage reduces left ventricular mass, improves diastolic function and increases contractility in hypertensive left ventricular hypertrophy (LVH). We planned to detect the effect of angiotensin receptor blockage on midwall mechanics and myocardial dynamics in hypertensive patients with LVH. METHODS: Angiotensin 2 type 1 receptor blocker (valsartan 80-160 mg) was administered to 38 previously untreated hypertensive patients with LVH for 6 months. Left ventricular midwall mechanics and tissue Doppler velocities were measured at baseline and at the end of the study. RESULTS: Mean blood pressure was reduced from 152 ±â€Š14/92 ±â€Š8 to 131 ±â€Š14/83 ±â€Š9 mmHg (P < 0.05). Left ventricular mass index was decreased from 135 ±â€Š15 to 114 ±â€Š14 g/m(2) (P < 0.001). Midwall fractional shortening was increased from 19.0 ±â€Š4 to 22.4 ±â€Š3% (P < 0.05). Circumferential end-systolic wall stress was decreased from 131 ±â€Š44 to 119 ±â€Š37 × 10(3) dyn/cm(2) (P < 0.05). Left ventricular interventricular septal myocardial tissue peak systolic velocity was increased from 6.7 ±â€Š1 to 8.1 ±â€Š0.9 cm/s (P < 0.001) and lateral wall myocardial tissue peak systolic velocity was increased from 7.5 ±â€Š1 to 9.0 ±â€Š1 cm/s (P < 0.001), and E/E(m) ratio was significantly decreased (11.0 ±â€Š0.3 to 8.90 ±â€Š0.1, P < 0.05) with 6-month valsartan therapy. CONCLUSION: This study suggests that valsartan exhibits not only blood pressure-lowering qualities but also cardioprotective actions in patients with hypertension because it enhances regression of LVH and improves left ventricular myocardial contractility and relaxation.