Quirino Ciampi

Myocardial Collagen Turnover in Hypertrophic Cardiomyopathy

Background—Myocardial interstitial fibrosis is a characteristic of hypertrophic cardiomyopathy (HCM). This study evaluates the collagen turnover in HCM and its impact on left ventricular (LV) diastolic function. Methods and Results—Thirty-six HCM patients and 14 sex- and age-matched controls were studied. Collagen turnover was assessed as follows. By radioimmunoassay, a byproduct of collagen III synthesis (PIIINP) and 3 peptides resulting from collagen I synthesis (PICP and PINP) and degradation (ICTP) were measured. By ELISA, matrix metalloproteinases (MMPs) were determined, as follows: active MMP-2; active MMP-9; and MMP-1 as active, free (as active MMP-1 plus its precursor), and total (as free MMP-1 plus MMP-1/tissue inhibitor complexes). Tissue inhibitor of metalloproteinases-1 (TIMP-1) was also assayed. All patients underwent echocardiography. The difference in duration between transmitral forward (A) and pulmonary venous retrograde (AR) waves (A−Ar) was considered an estimate of passive diastolic function. Furthermore, restrictive or pseudonormal LV filling patterns were considered to identify patients with passive diastolic dysfunction. Patients had higher levels of PIIINP, ICTP, MMP-2, MMP-9, and total TIMP-1 than did controls. PIIINP was inversely related to LV end-diastolic diameter. A−Ar was inversely related to PICP, PINP, and their differences with ICTP (estimates of collagen I buildup). Furthermore, A−Ar was directly related to MMP-1 and MMP-2. Conclusions—As compared with controls, collagen turnover is enhanced in HCM patients. As collagen I synthesis prevails over degradation and MMP-1 and MMP-2 are inhibited, passive diastolic dysfunction occurs in patients with HCM.

Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function

Some studies have demonstrated that left ventricular (LV) diastolic function is the principal determinant of impaired exercise capacity in hypertrophic cardiomyopathy (HC). In this study we sought the capability of echocardiographic indexes of diastolic function in predicting exercise capacity in patients with HC. We studied 52 patients with HC while they were not on drugs;12 of them had LV tract obstruction at rest. Diastolic function was assessed by M-mode and Doppler echocardiography by measuring: (1) left atrial fractional shortening, and the slope of posterior aortic wall displacement during early atrial emptying on M-mode left atrial tracing; and (2) Doppler-derived transmitral and pulmonary venous flow velocity indexes. Exercise capacity was assessed by maximum oxygen consumption by cardiopulmonary test during cycloergometer upright exercise. Maximum oxygen consumption correlated with the left atrial fractional shortening (r = 0.63, p <0.001), the slope of posterior aortic wall displacement during early atrial emptying (r = 0.55, p <0.001), age (r = -0.50; p <0.001), pulmonary venous diastolic anterograde velocity (r = 0.41, p <0.01), and the systolic filling fraction (r = -0.43; p <0.01). By stepwise multiple linear regression analysis, left atrial fractional shortening and the pulmonary venous systolic filling fraction were the only determinants of the maximum oxygen consumption (multiple r = 0.70; p <0.001). Exercise capacity did not correlate with Doppler-derived transmitral indexes. Thus, in patients with HC, exercise capacity was determined by passive LV diastolic function, as assessed by the left atrial M-mode and Doppler-derived pulmonary venous flow velocities.

Hemodynamic determinants of exercise-induced abnormal blood pressure response in hypertrophic cardiomyopathy

OBJECTIVES We sought to assess the hemodynamics of exercise in patients with hypertrophic cardiomyopathy (HCM), with and without an exercise-induced abnormal blood pressure (BP) response, by ambulatory radionuclide monitoring of left ventricular (LV) function with the VEST device (Capintec Inc., Ramsey, New Jersey). BACKGROUND Blood pressure fails to increase >20 mm Hg during exercise in about one-third of patients with HCM. This carries a high risk of sudden death. METHODS Forty-three patients with HCM and 14 control subjects underwent maximal symptom-limited exercise on a treadmill during VEST. The VEST data were averaged for 1 min and analyzed at baseline, 3 min and peak exercise. The LV end-diastolic, end-systolic and stroke volumes, cardiac output and systemic vascular resistance were expressed as the percentage of baseline. RESULTS Ejection fraction and stroke volume fell in patients with HCM, although they increased in control subjects (p < 0.001 and p = 0.002, respectively). Cardiac output increased significantly more in control subjects than in patients with HCM (p = 0.001). In 17 patients with HCM (39%) with an abnormal BP response, ejection fraction and stroke volume fell more (p = 0.032 and p = 0.009, respectively) and cardiac output increased less (p = 0.001) than they did in patients with HCM with a normal BP response. Systemic vascular resistance decreased similarly in patients with HCM, irrespective of the BP response. CONCLUSIONS In patients with HCM with and without an abnormal BP response, abnormal hemodynamic adaptation to exercise was qualitatively similar but quantitatively different. An abnormal BP response was associated with exercise-induced LV systolic dysfunction. This causes hemodynamic instability, associated with a high risk of sudden cardiac death.

Chronobiological Patterns of Onset of Tako-Tsubo Cardiomyopathy: A Multicenter Italian Study

To the Editor: Several cardiovascular events, including acute myocardial infarction (AMI), show well-defined temporal patterns in their occurrence throughout the year and the day ([1,2][1]). Tako-Tsubo cardiomyopathy (TTC), also called “stress cardiomyopathy” or “transient left ventricular

Differences in Clinical Features and In‐Hospital Outcomes of Older Adults with Tako‐Tsubo Cardiomyopathy

To describe the clinical characteristics and in‐hospital outcomes of older adults with tako‐tsubo cardiomyopathy (TTC).

Identification of responders to cardiac resynchronization therapy by contractile reserve during stress echocardiography

The identification of responders to cardiac resynchronization therapy (CRT) remains a challenge. We assessed the role of dyssynchrony (DYS) and contractile reserve (CR) in identifying CRT responders.

Echocardiographic assessment of regional left ventricular wall motion abnormalities in patients with tako-tsubo cardiomyopathy: comparison with anterior myocardial infarction

AIMS The aim of this study was to assess the echocardiographic distribution of regional wall motion abnormalities (RWMA) in patients with tako-tsubo cardiomyopathy (TTC) compared with anterior ST-elevation myocardial infarction (ant-STEMI). METHODS AND RESULTS Thirty-seven TTC and 37 ant-STEMI patients underwent standard echocardiographic examination at the time of hospital admission. RWMA and the involvement of the left ventricular territories supplied by each coronary artery according to the American Society of Echocardiography classification were reported. TTC patients showed a lower left ventricular ejection fraction (37.6 ± 5.1 vs. 40.9 ± 3.7%; P = 0.002) and a higher wall motion score index (WMSI; 1.98 ± 0.2 vs. 1.51 ± 0.14; P < 0.001) compared with ant-STEMI patients. No significant differences were observed between groups with regard to detection of RWMA in the territory supplied by the left anterior descending coronary artery (LAD) (37 vs. 37; P = 1). Conversely, in TTC patients, the territories supplied by the LAD/left circumflex coronary artery (LCX) (37 vs. 31; P = 0.011), LAD/right coronary artery (RCA) (34 vs. 13; P < 0.001), RCA (33 vs. 5; P < 0.001), and RCA/LCX (31 vs. 2; P < 0.001) were more frequently involved. A cut-off value of WMSI ≥1.75 (area under the curve 0.956) and for the number of territories with RWMA ≥4 (AUC = 0.928) predicted TTC with a sensitivity of 83 and 84% and a specificity of 100 and 97%, respectively. CONCLUSION Echocardiography revealed a distinctive pattern of contractility in TTC patients, characterized by symmetrical RWMA extending equally into the territory of distribution of all coronary arteries.

Effects of Diltiazem on Left Ventricular Systolic and Diastolic Function in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) is characterized by impaired diastolic function, and left ventricular (LV) outflow tract obstruction in about one-fourth of patients. Verapamil improves diastolic properties, but may have dangerous adverse effects. This study investigates the effects of diltiazem on hemodynamics and LV function in 16 patients with HC who were studied with cardiac catheterization and simultaneous radionuclide angiography. Studies were performed during atrial pacing (15 beats above spontaneous rhythm) at baseline and during intravenous diltiazem administration (0.25 mg x kg(-1) over 2 minutes, and 0.014 mg x kg(-1) x min(-1). Diltiazem induced a systemic vasodilation (cardiac index: 3.4 +/- 1.0 to 4.0 +/- 1.0 L x min(-1) x m(-2), p = 0.003; aortic systolic pressure: 116 +/- 16 to 107 +/- 19 mm Hg, p = 0.007; systemic resistance index: 676 +/- 235 to 532 +/- 193 dynes x s x cm(-5) x m(-2), p = 0.006), not associated with changes in the LV outflow tract gradient. The end-systolic pressure/volume ratio decreased (30 +/- 42 to 21 +/- 29 mm Hg x ml(-1) x m(-2); p = 0.044). Pulmonary artery wedge pressure (11 +/- 5 to 15 +/- 6 mm Hg, p = 0.006), and peak filling rate increased (4.1 +/- 1.3 to 6.0 +/- 2.4 stroke counts x s(-1), p = 0.004). The time constant of isovolumetric relaxation tau decreased (74 +/- 40 to 59 +/- 38 ms, p = 0.045). The constant of LV chamber stiffness did not change. Thus, active diastolic function is improved by the acute administration of diltiazem by both direct action and changes in hemodynamics and loading conditions. LV outflow tract gradient does not increase despite systemic vasodilation. In some patients, however, a marked increase in obstruction and a potentially harmful elevation in pulmonary artery wedge pressure do occur. Passive diastolic function is not affected.

Monday preference in onset of takotsubo cardiomyopathy

OBJECTIVE Acute cardiovascular events show definite temporal patterns of occurrence. Takotsubo cardiomyopathy (TTC) has been recently shown to exhibit a seasonal (summer) and circadian (morning) temporal distribution. The aim of this study, based on the database of a multicenter Italian network, was to investigate the possible existence of a weekly pattern of onset of TTC. METHODS The study included all cases of TTC admitted to the coronary care unit of 8 referral cardiac centers in Italy (five in Southern Italy and three in Northern Italy, respectively), belonging to the Takotsubo Italian Network (January 2002-December 2008). Day of admission was categorized into seven 1-day intervals according by week, and chronobiological analysis was performed by partial Fourier series. RESULTS The database included 112 patients with TTC (92.9% females). The weekly distribution identified the highest number of cases on Monday and the lowest on Saturday. Chronobiologic analysis yielded a rhythmic pattern with a significant peak on Monday (P = .036). CONCLUSIONS This study confirms a Monday preference for TTC occurrence on Monday, similar to that reported for acute myocardial infarction. Stress of starting weekly day life activities, could play a triggering role.

End-Systolic Elastance and Ventricular-Arterial Coupling Reserve Predict Cardiac Events in Patients with Negative Stress Echocardiography

Background. A maximal negative stress echo identifies a low-risk subset for coronary events. However, the potentially prognostically relevant information on cardiovascular hemodynamics for heart-failure-related events is unsettled. Aim of this study was to assess the prognostic value of stress-induced variation in cardiovascular hemodynamics in patients with negative stress echocardiography. Methods. We enrolled 891 patients (593 males mean age 63 ± 12, ejection fraction 48 ± 17%), with negative (exercise 172, dipyridamole 482, and dobutamine 237) stress echocardiography result. During stress we assessed left ventricular end-systolic elastance index (E LVI), ventricular arterial coupling (VAC) indexed by the ratio of the E LVI to arterial elastance index (E aI), systemic vascular resistance (SVR), and pressure-volume area (PVA). Changes from rest to peak stress (reserve) were tested as predictors of main outcome measures: combined death and heart failure hospitalization. Results. During a median followup of 19 months (interquartile range 8–36), 50 deaths and 84 hospitalization occurred. Receiver-operating-characteristic curves identified as best predictors E LVI reserve for exercise (AUC = 0.871) and dobutamine (AUC = 0.848) and VAC reserve (AUC = 0.696) for dipyridamole. Conclusions. Patients with negative stress echocardiography may experience an adverse outcome, which can be identified by assessment of E LVI reserve and VAC reserve during stress echo.