Resident cardiac stem cells.

The introduction of stem cells in cardiology provides new tools in understanding the regenerative processes of the normal and pathologic heart and opens new options for the treatment of cardiovascular diseases. The feasibility of adult bone marrow autologous and allogenic cell therapy of ischemic cardiomyopathies has been demonstrated in humans. However, many unresolved questions remain to link experimental with clinical observations. The demonstration that the heart is a self-renewing organ and that its cell turnover is regulated by myocardial progenitor cells offers novel pathogenetic mechanisms underlying cardiac diseases and raises the possibility to regenerate the damaged heart. Indeed, cardiac stem progenitor cells (CSPCs) have recently been isolated from the human heart by several laboratories although differences in methodology and phenotypic profile have been described. The present review points to the potential role of CSPCs in the onset and development of congestive heart failure and its reversal by regenerative approaches aimed at the preservation and expansion of the resident pool of progenitors.

A randomised comparison of the use of 4 and 6 French diagnostic catheters: the limits of downsizing.

BACKGROUND: The use of small catheters for coronary angiography can reduce the risk of vascular complications and allow early ambulation, but excessive downsizing may lead to poor quality imaging. The aim of this study was to assess the feasibility of performing coronary angiography using 4 French (4 F) femoral catheters. METHODS: In total, 400 consecutive elective patients were randomised to undergo coronary angiography with 4 F or 6 F catheters. The puncture site was manually compressed and inspected before and after ambulation, and 24 h later. The handling difficulty of the catheters was semi-quantitatively evaluated using a three grade scoring system; angiogram quality was evaluated by two independent physicians. RESULTS: No major procedure-related complications were observed. Coronary arteriography with 4 F catheters was possible in all of the attempted cases. There were no statistical differences between the two groups in terms of procedural or fluoroscopy time, the amount of contrast medium used, or the incidence of vascular complications, while compression time was significantly shorter in the patients studied using the smaller catheter (3.4 vs. 9.9 min; P<0.0001). Catheter stability was similar in the two groups, whereas catheter torque and the quality of the coronary angiograms were statistically better in the patients studied using six French catheters. CONCLUSIONS: Coronary angiography with 4 F catheters is technically feasible and permits early ambulation after the procedure. Although the radiological resolution of the images obtained using 4 F catheters was always adequate for clinical decision-making, the angiogram quality and catheter handling were significantly better using the 6 F system.

Acute stent recoil: in vivo evaluation of different stent designs.

This study sought to investigate the degree of acute recoil of four different stents by means of quantitative coronary angiography. Four hundred and six patients underwent stent implantation for single discrete coronary artery lesion: 105 received a 16 mm Paragon stent, 112 an 18 mm Multilink Duet, 97 a 16 mm NIR Primo stent, and 92 a 15 or 18 mm NIR Royal Advance. Elastic recoil was defined as the difference between mean balloon cross-sectional area (CSA) at the highest pressure and mean CSA after PTCA. The mean stent recoil was 13% +/- 10% CSA (P < 0.001), being statistically greater for the nitinol Paragon stent (21% +/- 11%), intermediate for the multicellular Multilink Duet stent (14% +/- 7%), and minimum for the NIR family (9% +/- 6% and 8% +/- 7%, respectively). The recoil was not homogeneously distributed along the stent length but was lower at the two ends (11% +/- 12% and 13% +/- 11%) and highest in the central part (15% +/- 12%)(P < 0.001). Thus, acute recoil is a significant phenomenon regardless of the mechanical properties and design of new-generation tubular stents.

Stent implantation without predilation in patients with a single, noncalcified coronary artery lesion.

The purpose of this study was to assess the feasibility of stent implantation without predilation in patients with a single, noncalcified coronary artery lesion. A total of 122 patients were randomized to receive a stent with or without predilation; direct stent placement was possible in 59 of the 61 patients (97%) with an immediate and long-term clinical follow-up similar to that observed in the group of patients treated conventionally.

Prognostic indices in heart transplant candidates after the first hospitalization triggered by the need for intravenous pharmacologic circulatory support.

BACKGROUND: Patients with heart failure refractory to optimal oral pharmacologic therapy have a dismal short term prognosis. Heart transplantation is the only therapy shown to improve survival in these patients. Unfortunately, due to the critical shortage of donor organs, approximately 30% of listed patients with end-stage heart failure die before a suitable donor heart becomes available. The principal aim of this study was to determine whether intravenous pharmacologic circulatory support favorably influences the clinical course of heart transplant candidates or whether mechanical circulatory support should be instituted in this high risk patient population. METHODS: Data from 154 consecutive hospitalizations in 125 patients 49+/-12 years were retrospectively reviewed. The product limit method was used to estimate survival. Multiple logistic regression analysis was used to identify the clinical and hemodynamic variables that independently predict outcome after each admission in which heart transplantation did not occur. RESULTS: One year survival for the study population was 65%. This survival is significantly lower than the 91% 1 year survival in similarly ill patients undergoing heart transplantation. The Cox proportional hazard method identified serum bilirubin, blood urea nitrogen (BUN), serum sodium levels and right atrial pressure as independent prognostic indices. Serum bilirubin, BUN levels and duration of intravenous pharmacologic circulatory support were associated with a poor outcome. A composite index including serum bilirubin and BUN levels predicted outcome with a sensitivity and specificity of 79% and 77%, respectively. The addition of pharmacologic support duration increased the model's sensitivity to 95%, but did not significantly alter specificity that was 74%. Of the 125 patients hospitalized due to the need to initiate intravenous pharmacologic support for the first time (index hospitalization), 69 (55%) were discharged after optimization of medical therapy. Of 21 patients who did not undergo transplantation during the follow-up period, 18 (86%) died within 2 years of the index hospitalization. The duration of intravenous pharmacologic support beyond which prognosis dramatically worsens without heart transplantation is 21 days. CONCLUSION: Heart transplant candidates who require intravenous pharmacologic circulatory support for more than 21 days and do not receive a suitable donor heart within this period of time have a high mortality. Alternative therapies, such as implantation of a mechanical circulatory assist device should be considered in this high risk population.

[The hemodynamics laboratory without cine film. A comparison between the production costs of 35-mm film and the recordable compact disk]. / Il laboratorio di emodinamica cineless. Confronto tra costi di produzione del film 35 mm e del compact disk recordable.

BACKGROUND: For more than 35 years, cine film has been used as the standard recording medium for coronary angiography. At present, the DICOM and the CD-R format have been established as the standard media for the transport of cardiac angiographic images in place of cine angiographic film. The aim of the study was to compare the media production costs between two cardiac catheterization laboratories, with and without cine film. METHODS: We collected data from two different laboratories in the same geographic area which perform about 1000 procedures/year, using a similar digital x-ray imaging system. In one lab, images are recorded on 35-mm film at 25 frames/sec. In the other one, the image support is based on a CD-R. For each laboratory we considered both direct patient and variable equipment costs. Direct patient costs in the film-lab include: cine film, processing chemicals, processing labor, chemical disposal, maintenance; in the digital lab: CD-R costs and masterization time. Equipment costs in the film-lab include: cine camera, cine film processor and cine projector; in the filmless lab a DICOM formatter and a review workstation. The equipment amortization costs are considered over a three-year period. RESULTS: Total direct patient costs are 90,000 lira for the film and 14,000 lira for the CD-R. Equipment costs are 193,000,000 lira in the film-lab and 150,000,000 lira in the filmless one. Overall cost per patient is 154,300 lira for the cine film and 64,000 lira for the CD-R. CONCLUSIONS: This study shows that the media costs per patient for a digital DICOM CD-R format system are substantially less than for 35-mm film, permitting savings of more than 90,000,000 Italian lira per year in a mid-volume cardiac catheterization laboratory.

Combined heart and kidney transplantation: an effective therapeutic option--report of six cases.

Six cases of combined heart and kidney transplantation with organs from the same donor are reported. All six patients suffered from primary end-stage kidney disease, two chronic glomerulonephritis, two glomerulosclerosis, one chronic pyelonephritis and one with unknown etiology. Four patients were undergoing hemodialysis. Three patients had the diagnosis of ischemic heart disease, one dilated cardiomyopathy secondary to congenital heart disease, two idiopathic dilated cardiomyopathy. Five were males and one female. Ages ranged from 38 to 54 years. On-site or short-distance young donors with normal renal function and good cardiac function necessitating low inotropic support were selected. ABO compatibility was used exclusively. Orthotopic heart transplantation was performed first. During cardiopulmonary bypass, hemofiltration was used in four cases. Kidney transplantation was performed immediately after the closure of the chest. Diuresis was immediate in all cases. No cardiac rejection was documented at EMB. Renal function normalized within few days with no signs of kidney rejection. All six patients are alive and well with normal cardiac and renal function at a mean follow-up of 43 months. Patients and donors selection associated with a proper surgical strategy and prompt immunosuppressive therapy administration make the combined heart and kidney transplantation an effective therapeutic option.

Apoptosis in the failing human heart.

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.

Restrictive criteria for heart transplantation candidacy maximize survival of patients with advanced heart failure.

BACKGROUND: The shortage of organ donors and the amelioration of medical management of advanced heart failure mandate strict selection of heart transplant candidates on the basis of the need and probability of success of transplantation, with the aim of maximizing survival of patients with advanced heart failure, both with and without transplantation. This study analyzes the impact of restricting the criteria for heart transplantation candidacy on the outcome of patients with advanced heart failure referred for transplantation. METHODS: Survival and freedom from major cardiac events (death, resuscitated cardiac arrest, transplantation while supported with inotropes or mechanical devices) were compared between patients listed during 1990 to 1991, when standard criteria were applied (group 1, n = 118), and patients listed during 1993 to 1994, when only patients requiring continuous/recurrent intravenous inotrope therapy in spite of optimized oral medications and outpatients showing actual progression of the disease were admitted to the waiting list (group 2, n = 88). Survival and freedom from cardiac events (defined as above plus listing in urgent status) were also calculated in stable outpatients evaluated in 1993 to 1994, who were potential heart transplant candidates according to standard criteria but were not listed because of restrictive criteria (group 3, n = 52, New York Heart Association functional class > or = III, mean echocardiographic ejection fraction 0.22 +/- 0.05, mean peak oxygen consumption 12.3 +/- 1.5 ml/kg/min, mean follow-up 19 +/- 10 months). RESULTS: Thirty-one percent, 40%, and 50% of group 1 patients versus 58%, 65%, and 77% of group 2 patients underwent transplantation within 3, 6, and 12 months after listing (p < 0.0007). The 1- and 2-year survival rates after listing were 80% and 71% in group 1 versus 85% and 84% in group 2 (p < 0.0001). Freedom from death/urgent transplantation was lower in group 2 than in group 1 (55% and 48% versus 72% and 59% at 6 and 12 months, respectively; p < 0.0001). In patients undergoing transplantation, the postoperative survival rate was similar (87% and 91% at 2 years in group 1 and group 2, respectively). Two years after heart transplantation candidacy was denied, 86% of group 3 patients were alive, and 74% were event-free. CONCLUSIONS: Restricting the admissions to the waiting list to patients with refractory/progressive heart failure improved survival rates after listing by increasing the probability to undergo transplantation in a short time. Selection of most severely ill candidates did not affect postoperative survival. Survival and freedom from cardiac events were good in patients with advanced but stable heart failure, in spite of their severe functional limitation. Thus restrictive criteria for heart transplantation candidacy allows maximal survival benefit from both medical therapy and transplantation.

[Heart transplantation 1985-1995: 10 years experience at the "Angelo De Gasperis" center. Improvement of results by progress in operative criteria]. / Trapianto cardiaco 1985-1995: 10 anni di esperienza al Centro "Angelo De Gasperis". Miglioramento dei risultati mediante l'evoluzione dei criteri operativi.

BACKGROUND: At 10-years from beginning of transplant experience in our Center we analyzed the overall results in an attempt to identify risk factors for early (3 months) and late (over 3 months) mortality after heart transplantation (HTx). METHODS: The data of 313 patients transplanted from November 1985 to June 1995 were studied and analyzed with a multivariate logistic regression and Cox's proportional hazard model. Seventy pre, intra and postoperative variables were considered: demographics, clinical status, hemodynamic parameters, donor characteristics, donor-recipient mismatch, complications, immunosuppressive protocols. In this paper we compared results in patients operated on from 1985 to 1990 (Group I) and from 1991 to 1995 (Group II) in order to assess improvements due to changes in HTx indication and in perioperative treatments. RESULTS: Overall mortality in the entire group was 19.8% (62/313): 30-days, 3 months and late mortality rates were 8.0%, 10.2%, 10.7% respectively. In Group II mortality rates were 7.1%, 8.6% and 2.8% respectively despite significant increase in Status I patients (21.5% in Group I vs 40.1% in Group II, p = 0.0008). Main causes of early death were: graft failure (46.9%), infection (28.1%), acute- rejection (12.5%). Main causes of late death were: cardiac allograft vasculopathy (40.0%) and neoplasm (23.3%). The mean follow-up of the 281 survivors more than 3 months is 45.6 +/- 30.0 months (range 3 to 120 months). Actuarial survival is 86.9 +/- 1.9%, 78.4 +/- 2.7% and 70.7 +/- 3.9% at 1, 5 and 10 years respectively. The difference in the 5-years actuarial survival between Group I and Group II patients is statistically significant (70.7 +/- 4.2% vs 84.5 +/- 4.5%, p = 0.005). TPG (OR 1.19), RAP (OR 1.13) and MD-HD inotropic support of donor (OR 3.81) were identified as independent risk factors for early mortality. Number of moderate rejection at biopsy (OR 1.56) and early postTx infection (OR 3.37) were identified as independent risk factors for late mortality. CONCLUSIONS: The overall results of our ten-year experience are very satisfying in relation to early and late mortality, with a significant favourable trend between patients transplanted in the early era (1985-1990) and those transplanted in the recent era (1991-1995). The study confirm that morbidity and mortality have the highest incidence during the early post-transplantation phase. Pulmonary hypertension and elevated preoperative right filling pressure appear to indicate a significantly increased risk of early death and only marginally influence late survival that is principally related to the severe postoperative complications. Differently from other observations, among the donor-related and recipient-donor matching variables, this analysis evidenced as significant only the need for MD-HD catecolamines during donor-management.

The Concerted Action 'Heart' European registry on clinical application of mechanical circulatory support systems: bridge to transplant. The Registry Scientific Committee.

OBJECTIVE: The goal of this paper is to identify in the field of mechanical support as bridge to transplant, by statistical analysis, variables influencing survival during support (transplanted patients) and the overall survival (discharged after transplant). METHODS: Clinical factors are analysed in 258 patients in the period 1986-1993. All variables were analyzed by a univariate and multivariate analysis. RESULTS: The indications for mechanically circulatory support were hemodynamic deterioration before transplantation in 177 (69%), post acute myocardial infarction in 40 (15%), postcardiotomy cardiogenic shock in 20 (8%), graft failure in 12 (5%) and cardiac rejection 9 (3%). The devices implanted have been: pneumatic VAD in 145 cases (56%), electromechanical LVAS in 15 cases (6%), TAH in 78 cases (30%) and centrifugal pumps in 20 cases (8%). The patients were supported for period ranging from 2 h to 623 days (mean 18.3 days +/- 43.2). The type of support was: LVAD 50 cases (20%), RVAD 3 cases (1%), BVAD 127 cases (49%), and TAH 78 cases (30%). Bleeding occurred in 84 patients (32.5%), infections in 83 patients (32.1%); 21 embolic complications were reported in 16 patients (6%). Renal failure occurred in 64 cases (25%) requiring dialysis in 33 (13%); respiratory failure in 47 cases (18%); neurological impairment was noted in 22 patients (9%). One hundred-sixty patients were transplanted (62%) and 104 ultimately discharged (40% out of total 258 patients and 65% out of 160 transplanted patients). Among postoperative parameters, renal failure, TAH, neurological impairment and infection shown statistical power. Some pre- and post-operative variables were identified as independent risk factors for overall mortality: age, indication for graft failure, all indications different from cardiomyopathy, neurological impairment, renal insufficiency, infection, bleeding and any type of support different from LVAD. The improvement in the success rate in the last 2 years is statistically significant (P = 0.0282) considering both the percentage of transplanted patients and of discharged patients. CONCLUSIONS: The results are encouraging if mechanical support is performed in patients with deterioration while awaiting transplant, when LVAD is feasible and effective, when an ideal timing of transplant during support period is identified.

[Short-term survival after heart transplantation: the relationships between preoperative hemodynamics, organ function and postoperative clinical events]. / Sopravvivenza a breve termine dopo trapianto cardiaco: relazioni tra emodinamica preoperatoria, funzione d'organo, ed eventi clinici postoperatori.

AIM OF THE STUDY: Pulmonary hypertension is known to affect prognosis of cardiac allograft recipients. Aim of this study is to elucidate the mechanisms relating preoperative hemodynamics to early post-transplant mortality. METHODS: Hemodynamic and pre- and postoperative clinical data of 122 heart transplant recipients were reviewed with respect to early mortality (within 1 month or in-hospital). The relationships between hemodynamics and mortality were studied by means of univariate and multivariate analysis of absolute data and at different cut-off values of hemodynamic parameters. RESULTS: The following hemodynamic parameters were significantly different between survivors (n = 107) and non-survivors (n = 15): right atrial pressure (7.7 +/- 4.7 vs. 12.1 +/- 8.6 mm Hg, p < 0.004), pulmonary vascular resistance (2.57 +/- 1.44 vs. 3.72 +/- 1.88 Wood units, p < 0.007), pulmonary vascular resistance index (4.43 +/- 2.53 vs. 6.53 +/- 3.28 Wood units x m2, p < 0.005), and transpulmonary gradient (8.8 +/- 4.8 vs. 12.3 +/- 6.4 mm Hg, p < 0.02). Right atrial pressure and pulmonary vascular resistance index showed an independent value at stepwise multiple logistic regression analysis (p < 0.008 and < 0.03 respectively). When mortality was tested using cut-off values, it was significantly higher with right atrial pressure > or = 12 (7/28 vs 8/94, p < 0.05), pulmonary vascular resistance index > or = 8 (6/13 vs 9/109, p < 0.0005), and transpulmonary gradient > or = 15 (5/13 vs 10/109, p < 0.01). High right atrial pressure, pulmonary vascular resistance index, and transpulmonary gradient were associated with higher preoperative bilirubin (p < 0.03), which was significantly superior in non-survivors (1.44 +/- 1.53 vs. 0.83 +/- 0.61 mg/dl, p < 0.02). Postoperatively, severe right ventricular failure, severe renal failure and infections within 1 month were all strongly associated with an increased mortality (p < 0.00003); they were more common in patients with high preoperative right filling pressure (9% vs. 43%, p < 0.00002) and/or high pulmonary vascular resistance index (14% vs. 38%, p < 0.03), in those with high right atrial pressure (9% vs. 35%, p < 0.0009), and in those with high pulmonary vascular resistance index (17% vs. 58%, p < 0.002) respectively. Mortality after acute rejection within 1 month was significantly higher in patients with high preoperative right atrial pressure (8% vs. 57%, p < 0.006). CONCLUSIONS: Besides pulmonary hypertension, elevated preoperative right filling pressure appears to indicate an increased risk of early death after transplantation; pre- and postoperative end-organ dysfunction and post-transplant complications are more common or more threatening in this setting.

Hospital morbidity and mortality after myocardial revascularisation surgery: current changes in risk factors.

To identify the operating risks for mortality and morbidity in patients undergoing aortocoronary bypass surgery, the data of 514 myocardial revascularisation procedures performed consecutively between January 1991 and December 1992 were analysed; 73.2% of the patients had associated diseases and 59.3% had suffered one or more previous myocardial infarctions. The mean ejection fraction of the population as a whole was 52.2 +/- 13. In 10.5% of the cases there was severe left ventricular (LV) function impairment with a mean ejection fraction (EF) of 30.2 +/- 4.4 (range 20-35). A major preoperative complication occurred in 8.2% of the entire population and 68.8% of the patients undergoing emergency surgery. Surgery was elective in 72.7% of the cases, urgent in 15.4% and emergency in 11.9%. Hospital mortality was 4.1% (CL 3.2-4.9). In the group of electively operated patients, mortality was 2.7% (CL 1.8-3.5), with no statistically significant difference (P = 0.943) from the mortality observed in the patients undergoing urgent surgery [2.5% (CL 0.8-4.1)]. The mortality in both groups was statistically different (P = 0.0001 and P = 0.008) from that of the patients undergoing emergency surgery [14.7% (CL 10.1-18.9)]. Perioperative acute myocardial infarction occurred in 5.4% of the patients (CL 4.4-6.4), in three cases resulting in death [10.7% (CL 4.8-15.8)]. Fourteen of the acute myocardial infarctions (AMI) occurred in the 42 patients undergoing emergency surgery for acute coronary occlusion (33.3%). A percentage of 18.7% of the 493 surviving patients suffered a postoperative complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Extrathoracic ectopia cordis. Case report.

Extrathoracic ectopia cordis is a challenging congenital anomaly: surgical repair is generally unsuccessful because of the magnitude of the deformity and the associated intracardiac anomalies. Our clinical case had additional surgical risk for prematurity. Immediately after birth the mediastinal space was surgically enlarged and the naked heart covered with a prosthetic patch. Complete repair (placement of the heart inside the chest) would have been done later. The newborn infant survived the 1st procedure; unfortunately few hours later he died for not cardiac-related causes. Surgical strategies on this topic are discussed.

End-stage cardiac failure in humans is coupled with the induction of proliferating cell nuclear antigen and nuclear mitotic division in ventricular myocytes.

Proliferating cell nuclear antigen (PCNA) is a late growth-regulated gene that is expressed at the G1-S boundary of the cell cycle and is required for DNA synthesis and cell proliferation. Since quantitative results suggest that myocyte hyperplasia occurs in the decompensated human heart, we postulated that induction of the PCNA gene may be present in the failing heart in humans. PCNA protein was detected in myocardial samples obtained from the left and right ventricles of patients with congestive heart failure. Endomyocardial biopsies collected from donor subjects were used as control tissue. The percentage of positively stained myocyte nuclei in the ventricles was established by using PCNA monoclonal antibody and the immunoperoxidase technique. The localization of PCNA in myocytes was confirmed by alpha-sarcomeric actin antibody staining. PCNA labeling was present in left ventricular myocytes of 29 of the 32 hearts examined. In the right ventricle, 24 of the 29 samples showed positive staining. In a subset of 25 patients, the percentage of PCNA-labeled myocyte nuclei was measured and found to constitute 49 +/- 22% of left ventricular myocytes. A similar analysis for the right ventricle, conducted in 21 patients, showed that 49 +/- 19% of the myocyte nuclei exhibited PCNA protein. In addition, mitotic figures in myocytes were documented. A quantitative analysis of this cellular process revealed that 11 myocyte nuclei per 1 million cells exhibited mitotic images in chronic heart failure. Immediately after myocardial infarction, two cells per million showed mitotic division, and this phenomenon was restricted to the region adjacent to the necrotic tissue. No PCNA labeling or nuclear mitotic images were detected in the ventricular myocardium of control subjects. Thus, the observation that diffuse PCNA labeling and myocyte mitotic division are present in hearts with end-stage failure strongly suggests that adult ventricular myocytes are not terminally differentiated cells and that myocyte cellular hyperplasia may constitute a growth reserve mechanism of the diseased heart.